A human monoclonal anti-TNF alpha antibody (adalimumab) reduces airway inflammation and ameliorates lung histology in a murine model of acute asthma

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Nam, M.R. Park, H.J. Nam, S.K. Lee, K.H. Kim, M.S. Roh, S.-J. Um, C.-H. Son" "autores" => array:8 [ 0 => array:2 [ "nombre" => "Y.H." "apellidos" => "Nam" ] 1 => array:2 [ "nombre" => "M.R." "apellidos" => "Park" ] 2 => array:2 [ "nombre" => "H.J." "apellidos" => "Nam" ] 3 => array:2 [ "nombre" => "S.K." "apellidos" => "Lee" ] 4 => array:2 [ "nombre" => "K.H." "apellidos" => "Kim" ] 5 => array:2 [ "nombre" => "M.S." "apellidos" => "Roh" ] 6 => array:2 [ "nombre" => "S.-J." "apellidos" => "Um" ] 7 => array:2 [ "nombre" => "C.-H." 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Akelma, E. Mete, M.N. Cizmeci, M.K. Kanburoglu, D.D. Malli, D. Bozkaya" "autores" => array:6 [ 0 => array:2 [ "nombre" => "A.Z." "apellidos" => "Akelma" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Mete" ] 2 => array:2 [ "nombre" => "M.N." "apellidos" => "Cizmeci" ] 3 => array:2 [ "nombre" => "M.K." "apellidos" => "Kanburoglu" ] 4 => array:2 [ "nombre" => "D.D." "apellidos" => "Malli" ] 5 => array:2 [ "nombre" => "D." "apellidos" => "Bozkaya" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0301054613001870?idApp=UINPBA00004N" "url" => "/03010546/0000004300000001/v1_201501250943/S0301054613001870/v1_201501250943/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Original Article" "titulo" => "A human monoclonal anti-TNF alpha antibody (adalimumab) reduces airway inflammation and ameliorates lung histology in a murine model of acute asthma" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "14" "paginaFinal" => "18" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "F. Catal, E. Mete, C. Tayman, E. Topal, A. Albayrak, H. Sert" "autores" => array:6 [ 0 => array:3 [ "nombre" => "F." "apellidos" => "Catal" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 1 => array:3 [ "nombre" => "E." "apellidos" => "Mete" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "C." "apellidos" => "Tayman" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 3 => array:4 [ "nombre" => "E." "apellidos" => "Topal" "email" => array:1 [ 0 => "erdemtopal44@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 4 => array:3 [ "nombre" => "A." "apellidos" => "Albayrak" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "H." "apellidos" => "Sert" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Department of Pediatric Allergy and Asthma, Fatih University Faculty of Medicine, Ankara, Turkey" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Pediatric Allergy and Asthma, Gazi University Faculty of Medicine, Ankara, Turkey" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Pathology, Ankara Numune Education and Research Hospital, Ankara, Turkey" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Department of Anesthesia, Fatih University Faculty of Medicine, Ankara, Turkey" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1385 "Ancho" => 2100 "Tamanyo" => 625015 ] ] "descripcion" => array:1 [ "en" => "(1a and 1b) Normal alveoli and bronchi (control group), H&E ×40 and ×100. (2a) Peri-bronchiolar and perivascular mix inflammation (asthma group), H&E ×40. (2b) Thickened alveolar walls with inflammation (asthma group), H&E ×100. (3a) The lung parenchyma without inflammation (adalimumab-treated group), H&E ×40. (3b) Mild thickened alveolar septa (adalimumab-treated group), H&E ×100." ] ] ] "textoCompleto" => "IntroductionAsthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role.<a class="elsevierStyleCrossRef" href="#bib0005">1</a> Asthma is a T helper 2 (Th2)-mediated disease characterised by increased airway eosinophilia, goblet cell hyperplasia with associated mucus production, neutrophilia and increased numbers of lung macrophages and activated mast cells.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Additionally, cytokines play an important role in the aetiopathogenesis of asthma by promoting the development, differentiation, recruitment, activation and survival of inflammatory cells. TNF-alpha, which is a Th1 associated and pro-inflammatory cytokine with immunoregulatory activities, takes an important role in the aetiopathogenesis of asthma. TNF-alpha serves as a chemoattractant for the neutrophils and monocytes,<a class="elsevierStyleCrossRef" href="#bib0015">3</a> increases vascular permeability, and activates<a class="elsevierStyleCrossRef" href="#bib0020">4</a> T cells,<a class="elsevierStyleCrossRef" href="#bib0025">5</a> eosinophils<a class="elsevierStyleCrossRefs" href="#bib0015">3,6</a> and mast cells. Few experimental studies in asthma have determined that different TNF-alpha blocking agents (anti-TNF antibody, recombinant human TNF receptor p80 Fc fusion protein) reduced the inflammation in the airways.<a class="elsevierStyleCrossRefs" href="#bib0035">7,8</a> Additionally, data about the effects of human monoclonal anti-TNF alpha antibody seem to be limited. In the present study, the aim was to ascertain the effects of adalimumab (a human monoclonal anti-TNF alpha antibody) on lung histology and lung inflammation in a murine model of asthma.Materials and methodsAnimals and experimental designBALB/c (H-2d/d) female rats (n=18) were used for the study. Experimental protocols were approved by the Fatih University Animal Subject Committees. All animals were specified pathogen-free and were maintained under standard animal holding with water and food ad libitum at the Ankara D¿¿kap¿ Hospital, Research Center, Animals Research Laboratory in accordance with local and Turkish Home Office regulations. Twelve-week-old rats were randomly divided into three groups, including (group I) control (n=6) (Phosphate-buffered saline was implemented), (group II) asthma induced with OVA (n=6), and (group III) asthma induced with OVA+treated with adalimumab (n=6).Administration of OVA and adalimumab250¿l of “Phosphate-buffered saline” (PBS) was given intraperitoneally to the rats in the control group on the first day and 14th day of the study. Additionally, rats were administered 250¿l of PBS by intranasal route under anaesthesia (0.3ml ketamine (6.5mg/ml)/xylazine (0.44mg/ml, intraperitoneally) on the 14th, 25th, 26th and 27th days of the study. Rats in groups I and II were sensitised with intraperitoneal 1mg ovalbumin (OVA) (Sigma Co., St. Louis, MO) emulsified in 250¿l of PBS on the first and the 14th day of the study; and 500¿g OVA in 250¿l of PBS by intranasal route (OVA challenge) was applied to the rats under anaesthesia (0.3ml ketamine (6.5mg/ml)/xylazine (0.44mg/ml, intraperitoneally) on the 14th, 25th, 26th and 27th days of the study. Also, 100¿g OVA in 100¿l of PBS was given intraperitoneally to all rats one hour before each intranasal administration. Adalimumab with a dose of 5mg/kg/day was applied intraperitoneally to the rats in the third group for five days, starting from the day before the first challenge. All rats were sacrificed by cervical dislocation on the 28th day of the study. Lung tissues were removed for the histopathological examination.Lung histology and scoringThe lung samples were fixed in 10% neutral buffered formalin, after the routine tissue monitorisation, the sections were obtained and stained with haematoxylin and eosin (H&E) and evaluated under light microscope. The lung sections from all groups were examined in a blinded fashion and lung inflammation was scored on the sections stained with H&E. All slides were evaluated over 10 consecutive fields at ×200 magnification. In order to be scored, each field had to contain a complete transection of at least one bronchiole less than half a field width in diameter, a blood vessel and an alveolar airway. Inflammatory cell infiltrate, i.e. the number and type of inflammatory cells present, was evaluated for the perivascular area, the bronchiolar epithelium and the peri-bronchiolar alveolar tissue. Inflammation was also scored on the basis of increased alveolar wall thickness. The scoring system used to assess inflammation is shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<a class="elsevierStyleCrossRef" href="#bib0045">9</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Statistical analysisStatistical analysis was performed by the Statistical Package for Social Sciences (SPSS) 15.0 software (SPSS Inc., Chicago, IL). Quantitative variables (lung score) were expressed in medians. The median score of groups were compared by using Kruskal–Wallis test. Mann–Whitney U test with Benferoni correction was used to evaluate the differences between groups. A two-sided p<0.05 was considered statistically significant.ResultsCell infiltration, inflammation and histological examinationWhen compared with the normal controls, dense inflammation was seen in the perivascular and peribronchiolar areas, including lymphocytes and eosinophils infiltration; and interstitial space (alveoli walls) was severely thickened due to intense inflammation in the lung tissues of asthma induced rats (median score: 4, p=0.02). Bronchial smooth muscle hypertrophy and oedema were observed in the lung tissues of asthma induced rats. In the group treated with adalimumab, the number of inflammatory cells surrounding the bronchi and bronchioles and alveolar wall thickness had a similar histomorphological appearance with the control group (median score: 1, p=0.52). Furthermore, when compared, peribronchial smooth muscle hypertrophy and oedema were similar between the control group and the adalimumab-treated group (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Statistically significant levels of the lung scores between the groups are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.<elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia>DiscussionIn the current study, we evaluated the effects of adalimumab (a human monoclonal anti-TNF alpha antibody) on the lung histology and lung inflammation in a murine model of asthma. We found that adalimumab treatment decreased the cell inflammation, and showed similar histological findings to the control group. These findings support the opinion that anti-TNF alpha antibody could be a promising agent in the treatment of asthma.Asthma is a disease mediated by Th2 cells, and specific cytokines such as IL4, IL-5, and IL-13 have important roles in the aetiopathogenesis of asthma.<a class="elsevierStyleCrossRef" href="#bib0050">10</a> TNF alpha, which is a Th1 lymphocyte-associated cytokine, has been shown to play an important role in the pathogenesis of asthma in the studies of both animals and humans.<a class="elsevierStyleCrossRefs" href="#bib0055">11,12</a> TNF-alpha, a strong pro-inflammatory cytokine, is mainly synthesised and stored by mast cells and alveolar macrophages in the lung, and it also has immune-regulatory properties.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> Furthermore, it contributes to the development of remodelling in asthma by affecting on fibroblasts and triggering the release of matrix metalloproteinase-9.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> Some studies on rats exposed to house dust and in patients with severe asthma have determined increased TNF-alpha expression in the airways.<a class="elsevierStyleCrossRefs" href="#bib0040">8,15,16</a> Therefore, some other studies have been conducted to ascertain the beneficial effects of TNF alpha inhibiting agents on both the animal models and patients with severe asthma. Additionally, some experimental studies have reported that agents inhibiting synthesis and activity of TNF-alpha decrease the infiltration of inflammatory cells in the airways.<a class="elsevierStyleCrossRefs" href="#bib0085">17–19</a> However, these agents have been reported to be ineffective through some other studies.<a class="elsevierStyleCrossRefs" href="#bib0100">20,21</a> Furthermore, results of these studies vary according to blocking of TNF alpha activities by different steps. Although Nam et al. have reported that using soluble TNF-alpha receptor in a rat model of asthma reduces eosinophil infiltration; they have declared that no beneficial effects have been found on the airway inflammation, when compared to the control group. In contrast, Kim et al.<a class="elsevierStyleCrossRef" href="#bib0110">22</a> have determined in an experimental model of asthma that TNF alpha antibodies have provided significant improvement on the pulmonary inflammation, bronchial hyper-responsiveness and pulmonary histology.Recently, TNF alpha blocking agents have already been successfully used in the treatment of chronic diseases such as Crohn and Romatoid arthritis.<a class="elsevierStyleCrossRef" href="#bib0115">23</a> Moreover, asthma is a chronic disease and TNF alpha is believed to have a major role in the pathogenesis of asthma. Therefore, TNF alpha blocking agents would provide favourable effects on the treatment of asthma. Some experimental studies related to asthma have unveiled the beneficial effects of TNF alpha blocking agents on the airway histology, cytokine levels in bronchoalveolar lavage (BAL), and bronchial hyper-responsiveness. However, few studies conducted on patients with severe asthma have indicated increased TNF alpha activity in BAL fluid and on the surface of peripheral blood monocytes.<a class="elsevierStyleCrossRefs" href="#bib0075">15,24</a> These patients were administered Etanercept (a soluble fusion protein combining two identical chains of the human p75 TNF receptors with an Fc portion of human IgG1) for 12 weeks. At the end of the treatment session, improvement on the asthma symptoms such as bronchial hyper-responsiveness, and pulmonary function tests has been determined.All in all, asthma is a chronic disease of the airway, and it may sometimes have a severe nature and be treatment-resistant. TNF-alpha, a cytokine associated with Th1, is known to play an important role in the pathogenesis of asthma. It is also known that TNF-alpha blocking agents have beneficial effects on the airway inflammation, lung histology, and asthma symptoms. Adalimumab (a human monoclonal anti-TNF alpha antibody) is a different TNF alpha blocking agent. In the present study, we have evaluated the effects of adalimumab (a human monoclonal anti-TNF alpha antibody) on the lung histology and lung inflammation in a murine model of asthma. The work presented in the current study shows that adalimumab treatment suppresses the airway inflammation, and provides improvement in histological findings in asthma. We may suggest that adalimumab is a promising alternative for the treatment of patients with severe asthma which is unresponsive to treatment.Conflicts of interestNo competing financial interests exist and there is no conflicts of interest for each author.Ethical disclosuresPatients’ data protectionConfidentiality of Data. The authors declare that no patient data appear in this article.Right to privacy and informed consentThe authors declare that no patient data appear in this article.Protection of human subjects and animals in researchThe authors declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres414317" "titulo" => array:5 [ 0 => "Abstract" 1 => "Background" 2 => "Method" 3 => "Result" 4 => "Conclusion" ] ] 1 => array:2 [ "identificador" => "xpalclavsec389957" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Animals and experimental design" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Administration of OVA and adalimumab" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Lung histology and scoring" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analysis" ] ] ] 4 => array:3 [ "identificador" => "sec0035" "titulo" => "Results" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0040" "titulo" => "Cell infiltration, inflammation and histological examination" ] ] ] 5 => array:2 [ "identificador" => "sec0045" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of interest" ] 7 => array:3 [ "identificador" => "sec0055" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Patients’ data protection" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Right to privacy and informed consent" ] 2 => array:2 [ "identificador" => "sec0070" "titulo" => "Protection of human subjects and animals in research" ] ] ] 8 => array:2 [ "identificador" => "xack123029" "titulo" => "Acknowledgements" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-07-19" "fechaAceptado" => "2013-11-14" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec389957" "palabras" => array:8 [ 0 => "Adalimumab" 1 => "Anti-TNF alpha" 2 => "Antibody" 3 => "Asthma" 4 => "Cytokine" 5 => "Inflammation" 6 => "Murine" 7 => "Ovalbumin" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "BackgroundA few experimental studies related to asthma have unveiled the beneficial effects of TNF alpha blocking agents on the airway histology, cytokine levels in bronchoalveolar lavage and bronchial hyper-responsiveness. In the current study, we aimed to assess the effect of adalimumab on the inflammation and histology of asthma in a murine model. MethodTwelve-week-old BALB/c (H-2d/d) female rats (n=18) were allocated into three groups, including (group I) control (phosphate-buffered saline was implemented), (group II) asthma induced with OVA (n=6), and (group III) asthma induced with OVA+treated with adalimumab (n=6). Rats were executed on the 28th day of the study. The lung samples were fixed in 10% neutral buffered formalin. Lung parenchyma, alveolus, peribronchial and perivascular inflammation were assessed. Lung pathological scoring was performed. ResultSeverity of lung damage was found to be reduced significantly in the asthma induced with OVA+treated with adalimumab group. When compared with the untreated group, adalimumab significantly reduced the inflammatory cells around the bronchi and bronchioles, and reduced inflammation of the alveolar wall and alveolar wall thickness as well (median score=1, p=0.52). Peribronchial smooth muscle hypertrophy and oedema were significantly reduced after adalimumab administration. ConclusionAdalimumab (a human monoclonal anti-TNF alpha antibody) therapy significantly reduced the severity of lung damage by decreasing cellular infiltration and improvement on the lung histology in a murine model of acute asthma." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1385 "Ancho" => 2100 "Tamanyo" => 625015 ] ] "descripcion" => array:1 [ "en" => "(1a and 1b) Normal alveoli and bronchi (control group), H&E ×40 and ×100. (2a) Peri-bronchiolar and perivascular mix inflammation (asthma group), H&E ×40. (2b) Thickened alveolar walls with inflammation (asthma group), H&E ×100. (3a) The lung parenchyma without inflammation (adalimumab-treated group), H&E ×40. (3b) Mild thickened alveolar septa (adalimumab-treated group), H&E ×100." ] ] 1 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col">Area scored (number of cells) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Score</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">3 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">4 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Perivascular compartment<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No infiltration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><20 cells \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><100 cells \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">>100 cells \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Bronchiolar epithelium \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No infiltration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><5 cells \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><10 cells \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">>10 cells \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Peri-bronchiolar alveolar tissue<a class="elsevierStyleCrossRef" href="#tblfn0010">b</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No infiltration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><20 cells \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><100 cells \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">>100 cells \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Alveolar walls<a class="elsevierStyleCrossRef" href="#tblfn0015">c</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No infiltration \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2–3 cells \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4–5 cells \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">>5 cells \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab646895.png" ] ] ] "notaPie" => array:3 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Cells around blood vessel walls." ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "b" "nota" => "Defined as sub-bronchiolar tissue, beneath basement membrane and smooth muscle, not immediately adjacent to a blood vessel." ] 2 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "c" "nota" => "Scores indicative of focal expansion of alveolar walls by that number of cells." ] ] ] "descripcion" => array:1 [ "en" => "Scoring system for assessing inflammation in a murine asthma model<a class="elsevierStyleCrossRef" href="#bib0045">9</a>" ] ] 2 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Comparison of the groups \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Median lung score (min–max) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">P value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Group1, Group 2 & Group 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (1–2), 4 (3–4) &1 (1–2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.001<a class="elsevierStyleCrossRef" href="#tblfn0020">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Group 1 & Group 2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (1–2) & 4 (3–4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.002<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Group 1 & Group 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 (1–2) & 1 (1–2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.523<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Group 2 & Group 3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 (3–4) & 1 (1–2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.003<a class="elsevierStyleCrossRef" href="#tblfn0025">b</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab646896.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0020" "etiqueta" => "a" "nota" => "p: Kruskal–Wallis test." ] 1 => array:3 [ "identificador" => "tblfn0025" "etiqueta" => "b" "nota" => "p: Mann–Whitney U test. Group 1: Control group, Group 2: Murine asthma model, Group 3: Murine asthma model-adalimumab treated group." ] ] ] "descripcion" => array:1 [ "en" => "Comparison of the groups according to lung score." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:24 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "(GINA) 2011. Available from: <a href="http://www.ginasthma.org/">http://www.ginasthma.org</a>" ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pathology of asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.C. Hogg" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "1993" "volumen" => "92" "paginaInicial" => "1" "paginaFinal" => "5" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8335845" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0015" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "TNF-alpha mediates recruitment of neutrophils and eosinophils during airway inflammation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "N.W. Lukacs" 1 => "R.M. Strieter" 2 => "S.W. Chensue" 3 => "M. Widmer" 4 => "S.L. Kunkel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Immunol" "fecha" => "1995" "volumen" => "154" "paginaInicial" => "5411" "paginaFinal" => "5417" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7730642" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0020" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "TNF mediates lung leak, but not neutrophil accumulation, in lungs of rats given IL-1 intratracheally" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B.M. Hybertson" 1 => "E.K. Jepson" 2 => "O.J. Cho" 3 => "J.H. Clarke" 4 => "Y.M. Lee" 5 => "J.E. Repine" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1164/ajrccm.155.6.9196104" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Crit Care Med" "fecha" => "1997" "volumen" => "155" "paginaInicial" => "1972" "paginaFinal" => "1976" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9196104" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0025" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNFalpha-mediated enhancement of T cell responses" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "P. Scheurich" 1 => "B. Thoma" 2 => "U. Ucer" 3 => "K. Pfizenmaier" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Immunol" "fecha" => "1987" "volumen" => "138" "paginaInicial" => "1786" "paginaFinal" => "1790" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3029221" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0030" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "TNF alpha is important in human lung allergic reactions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "T.B. Casale" 1 => "J.J. Costa" 2 => "S.J. Galli" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1165/ajrcmb.15.1.8679220" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Cell Mol Biol" "fecha" => "1996" "volumen" => "15" "paginaInicial" => "35" "paginaFinal" => "44" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8679220" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0035" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tumour necrosis factor-alpha blockade suppresses murine allergic airways inflammation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Hutchison" 1 => "B.S. Choo-Kang" 2 => "R.V. Bundick" 3 => "A.J. Leishman" 4 => "J.M. Brewer" 5 => "I.B. McInnes" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2249.2007.03509.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Immunol" "fecha" => "2008" "volumen" => "151" "paginaInicial" => "114" "paginaFinal" => "122" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17931392" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0040" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anti-tumor necrosis factor-alpha antibody treatment reduces pulmonary inflammation and methacholine hyper-responsiveness in a murine asthma model induced by house dust" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Kim" 1 => "L. McKinley" 2 => "S. Natarajan" 3 => "G.L. Bolgos" 4 => "J. Siddiqui" 5 => "S. Copeland" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2222.2005.02407.x" "Revista" => array:6 [ "tituloSerie" => "Clin Exp Allergy" "fecha" => "2006" "volumen" => "36" "paginaInicial" => "122" "paginaFinal" => "132" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16393274" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0045" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "FITC-induced murine pulmonary inflammation: CC10 up-regulation and concurrent Shh expression" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C.E. Fisher" 1 => "S.A. Ahmad" 2 => "P.M. Fitch" 3 => "J.R. Lamb" 4 => "S.E. Howie" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cellbi.2005.07.002" "Revista" => array:6 [ "tituloSerie" => "Cell Biol Int" "fecha" => "2005" "volumen" => "29" "paginaInicial" => "868" "paginaFinal" => "876" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16150617" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0050" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Beta-arrestin-2 regulates the development of allergic asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.K. Walker" 1 => "A.M. Fong" 2 => "B.L. Lawson" 3 => "J.D. Savov" 4 => "D.D. Patel" 5 => "D.A. Schwartz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI17265" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "2003" "volumen" => "112" "paginaInicial" => "566" "paginaFinal" => "574" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12925697" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0055" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Th1- and Th2-type cytokines regulate the expression and production of eotaxin and RANTES by human lung fibroblasts" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.M. Teran" 1 => "M. Mochizuki" 2 => "J. Bartels" 3 => "E.L. Valencia" 4 => "T. Nakajima" 5 => "K. Hirai" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1165/ajrcmb.20.4.3508" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Cell Mol Biol" "fecha" => "1999" "volumen" => "20" "paginaInicial" => "777" "paginaFinal" => "786" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10101011" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0060" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human monocyte chemoattractant protein (MCP)-4 is a novel CC chemokine with activities on monocytes, eosinophils, and basophils induced in allergic and nonallergic inflammation that signals through the CC chemokine receptors (CCR)-2 and -3" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "E.A. Garcia-Zepeda" 1 => "C. Combadiere" 2 => "M.E. Rothenberg" 3 => "M.N. Sarafi" 4 => "F. Lavigne" 5 => "Q. Hamid" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Immunol" "fecha" => "1996" "volumen" => "157" "paginaInicial" => "5613" "paginaFinal" => "5626" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8955214" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0065" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the humanmast cell as a source of these cytokines" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Bradding" 1 => "J.A. Roberts" 2 => "K.M. Britten" 3 => "M.N. Sarafi" 4 => "F. Lavigne" 5 => "Q. Hamid" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1165/ajrcmb.10.5.8179909" "Revista" => array:6 [ "tituloSerie" => "Am J Respir Cell Mol Biol" "fecha" => "1994" "volumen" => "10" "paginaInicial" => "471" "paginaFinal" => "480" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8179909" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0070" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human eosinophils release matrix metalloproteinase-9 on stimulation with TNF alpha" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "A. Schwingshackl" 1 => "M. Duszyk" 2 => "N. Brown" 3 => "R. Moqbel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Allergy Clin Immunol" "fecha" => "1999" "volumen" => "104" "paginaInicial" => "983" "paginaFinal" => "989" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10550743" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0075" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Tumour necrosis factor (TNF alpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.H. Howarth" 1 => "K.S. Babu" 2 => "H.S. Arshad" 3 => "L. Lau" 4 => "M. Buckley" 5 => "W. McConnell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/thx.2005.045260" "Revista" => array:6 [ "tituloSerie" => "Thorax" "fecha" => "2005" "volumen" => "60" "paginaInicial" => "1012" "paginaFinal" => "1018" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16166100" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0080" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human antitumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S.B. Hanauer" 1 => "W.J. Sandborn" 2 => "P. Rutgeerts" 3 => "R.N. Fedorak" 4 => "M. Lukas" 5 => "D. MacIntosh" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2005.11.030" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2006" "volumen" => "130" "paginaInicial" => "323" "paginaFinal" => "333" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16472588" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0085" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Interleukin-10 inhibits antigen-induced cellular recruitment into the airways of sensitized mice" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "C. Zuany-Amorim" 1 => "S. Haile" 2 => "D. Leduc" 3 => "C. Dumarey" 4 => "M. Huerre" 5 => "B.B. 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Maini" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Transplant Proc" "fecha" => "1998" "volumen" => "30" "paginaInicial" => "4126" "paginaFinal" => "4127" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9865320" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0120" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evidence of a role of tumor necrosis factor alpha in refractory asthma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.A. Berry" 1 => "B. Hargadon" 2 => "M. Shelley" 3 => "D. Parker" 4 => "D.E. Shaw" 5 => "R.H. 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Original Article

F. Catala,d, E. Metea, C. Taymana, E. Topalb,

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erdemtopal44@gmail.com

Corresponding author.

, A. Albayrakc, H. Sertd

a Department of Pediatric Allergy and Asthma, Fatih University Faculty of Medicine, Ankara, Turkey

b Department of Pediatric Allergy and Asthma, Gazi University Faculty of Medicine, Ankara, Turkey

c Department of Pathology, Ankara Numune Education and Research Hospital, Ankara, Turkey

d Department of Anesthesia, Fatih University Faculty of Medicine, Ankara, Turkey

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TNF-alpha, which is a Th1 associated and pro-inflammatory cytokine with immunoregulatory activities, takes an important role in the aetiopathogenesis of asthma. TNF-alpha serves as a chemoattractant for the neutrophils and monocytes,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> increases vascular permeability, and activates<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> T cells,<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> eosinophils<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,6</span></a> and mast cells. Few experimental studies in asthma have determined that different TNF-alpha blocking agents (anti-TNF antibody, recombinant human TNF receptor p80 Fc fusion protein) reduced the inflammation in the airways.<a class="elsevierStyleCrossRefs" href="#bib0035"><span class="elsevierStyleSup">7,8</span></a> Additionally, data about the effects of human monoclonal anti-TNF alpha antibody seem to be limited. In the present study, the aim was to ascertain the effects of adalimumab (a human monoclonal anti-TNF alpha antibody) on lung histology and lung inflammation in a murine model of asthma.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Animals and experimental design</span><p id="par0010" class="elsevierStylePara elsevierViewall">BALB/c (H-2<span class="elsevierStyleSup">d/d</span>) female rats (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>18) were used for the study. Experimental protocols were approved by the Fatih University Animal Subject Committees. All animals were specified pathogen-free and were maintained under standard animal holding with water and food ad libitum at the Ankara D¿¿kap¿ Hospital, Research Center, Animals Research Laboratory in accordance with local and Turkish Home Office regulations. Twelve-week-old rats were randomly divided into three groups, including (group I) control (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6) (Phosphate-buffered saline was implemented), (group II) asthma induced with OVA (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6), and (group III) asthma induced with OVA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>treated with adalimumab (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Administration of OVA and adalimumab</span><p id="par0015" class="elsevierStylePara elsevierViewall">250<span class="elsevierStyleHsp" style=""></span>¿l of &#8220;Phosphate-buffered saline&#8221; (PBS) was given intraperitoneally to the rats in the control group on the first day and 14th day of the study. Additionally, rats were administered 250<span class="elsevierStyleHsp" style=""></span>¿l of PBS by intranasal route under anaesthesia (0.3<span class="elsevierStyleHsp" style=""></span>ml ketamine (6.5<span class="elsevierStyleHsp" style=""></span>mg/ml)/xylazine (0.44<span class="elsevierStyleHsp" style=""></span>mg/ml, intraperitoneally) on the 14th, 25th, 26th and 27th days of the study. Rats in groups I and II were sensitised with intraperitoneal 1<span class="elsevierStyleHsp" style=""></span>mg ovalbumin (OVA) (Sigma Co., St. Louis, MO) emulsified in 250<span class="elsevierStyleHsp" style=""></span>¿l of PBS on the first and the 14th day of the study; and 500<span class="elsevierStyleHsp" style=""></span>¿g OVA in 250<span class="elsevierStyleHsp" style=""></span>¿l of PBS by intranasal route (OVA challenge) was applied to the rats under anaesthesia (0.3<span class="elsevierStyleHsp" style=""></span>ml ketamine (6.5<span class="elsevierStyleHsp" style=""></span>mg/ml)/xylazine (0.44<span class="elsevierStyleHsp" style=""></span>mg/ml, intraperitoneally) on the 14th, 25th, 26th and 27th days of the study. Also, 100<span class="elsevierStyleHsp" style=""></span>¿g OVA in 100<span class="elsevierStyleHsp" style=""></span>¿l of PBS was given intraperitoneally to all rats one hour before each intranasal administration. Adalimumab with a dose of 5<span class="elsevierStyleHsp" style=""></span>mg/kg/day was applied intraperitoneally to the rats in the third group for five days, starting from the day before the first challenge. All rats were sacrificed by cervical dislocation on the 28th day of the study. Lung tissues were removed for the histopathological examination.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Lung histology and scoring</span><p id="par0020" class="elsevierStylePara elsevierViewall">The lung samples were fixed in 10% neutral buffered formalin, after the routine tissue monitorisation, the sections were obtained and stained with haematoxylin and eosin (H&#38;E) and evaluated under light microscope. The lung sections from all groups were examined in a blinded fashion and lung inflammation was scored on the sections stained with H&#38;E. All slides were evaluated over 10 consecutive fields at &times;200 magnification. In order to be scored, each field had to contain a complete transection of at least one bronchiole less than half a field width in diameter, a blood vessel and an alveolar airway. Inflammatory cell infiltrate, i.e. the number and type of inflammatory cells present, was evaluated for the perivascular area, the bronchiolar epithelium and the peri-bronchiolar alveolar tissue. Inflammation was also scored on the basis of increased alveolar wall thickness. The scoring system used to assess inflammation is shown in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Statistical analysis</span><p id="par0025" class="elsevierStylePara elsevierViewall">Statistical analysis was performed by the Statistical Package for Social Sciences (SPSS) 15.0 software (SPSS Inc., Chicago, IL). Quantitative variables (lung score) were expressed in medians. The median score of groups were compared by using Kruskal&#8211;Wallis test. Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test with Benferoni correction was used to evaluate the differences between groups. A two-sided <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0.05 was considered statistically significant.</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Results</span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Cell infiltration, inflammation and histological examination</span><p id="par0030" class="elsevierStylePara elsevierViewall">When compared with the normal controls, dense inflammation was seen in the perivascular and peribronchiolar areas, including lymphocytes and eosinophils infiltration; and interstitial space (alveoli walls) was severely thickened due to intense inflammation in the lung tissues of asthma induced rats (median score: 4, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.02). Bronchial smooth muscle hypertrophy and oedema were observed in the lung tissues of asthma induced rats. In the group treated with adalimumab, the number of inflammatory cells surrounding the bronchi and bronchioles and alveolar wall thickness had a similar histomorphological appearance with the control group (median score: 1, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.52). Furthermore, when compared, peribronchial smooth muscle hypertrophy and oedema were similar between the control group and the adalimumab-treated group (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Statistically significant levels of the lung scores between the groups are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Discussion</span><p id="par0035" class="elsevierStylePara elsevierViewall">In the current study, we evaluated the effects of adalimumab (a human monoclonal anti-TNF alpha antibody) on the lung histology and lung inflammation in a murine model of asthma. We found that adalimumab treatment decreased the cell inflammation, and showed similar histological findings to the control group. These findings support the opinion that anti-TNF alpha antibody could be a promising agent in the treatment of asthma.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Asthma is a disease mediated by Th2 cells, and specific cytokines such as IL4, IL-5, and IL-13 have important roles in the aetiopathogenesis of asthma.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> TNF alpha, which is a Th1 lymphocyte-associated cytokine, has been shown to play an important role in the pathogenesis of asthma in the studies of both animals and humans.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,12</span></a> TNF-alpha, a strong pro-inflammatory cytokine, is mainly synthesised and stored by mast cells and alveolar macrophages in the lung, and it also has immune-regulatory properties.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Furthermore, it contributes to the development of remodelling in asthma by affecting on fibroblasts and triggering the release of matrix metalloproteinase-9.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Some studies on rats exposed to house dust and in patients with severe asthma have determined increased TNF-alpha expression in the airways.<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8,15,16</span></a> Therefore, some other studies have been conducted to ascertain the beneficial effects of TNF alpha inhibiting agents on both the animal models and patients with severe asthma. Additionally, some experimental studies have reported that agents inhibiting synthesis and activity of TNF-alpha decrease the infiltration of inflammatory cells in the airways.<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#8211;19</span></a> However, these agents have been reported to be ineffective through some other studies.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20,21</span></a> Furthermore, results of these studies vary according to blocking of TNF alpha activities by different steps. Although Nam et al. have reported that using soluble TNF-alpha receptor in a rat model of asthma reduces eosinophil infiltration; they have declared that no beneficial effects have been found on the airway inflammation, when compared to the control group. In contrast, Kim et al.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> have determined in an experimental model of asthma that TNF alpha antibodies have provided significant improvement on the pulmonary inflammation, bronchial hyper-responsiveness and pulmonary histology.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Recently, TNF alpha blocking agents have already been successfully used in the treatment of chronic diseases such as Crohn and Romatoid arthritis.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Moreover, asthma is a chronic disease and TNF alpha is believed to have a major role in the pathogenesis of asthma. Therefore, TNF alpha blocking agents would provide favourable effects on the treatment of asthma. Some experimental studies related to asthma have unveiled the beneficial effects of TNF alpha blocking agents on the airway histology, cytokine levels in bronchoalveolar lavage (BAL), and bronchial hyper-responsiveness. However, few studies conducted on patients with severe asthma have indicated increased TNF alpha activity in BAL fluid and on the surface of peripheral blood monocytes.<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15,24</span></a> These patients were administered Etanercept (a soluble fusion protein combining two identical chains of the human p75 TNF receptors with an Fc portion of human IgG1) for 12 weeks. At the end of the treatment session, improvement on the asthma symptoms such as bronchial hyper-responsiveness, and pulmonary function tests has been determined.</p><p id="par0050" class="elsevierStylePara elsevierViewall">All in all, asthma is a chronic disease of the airway, and it may sometimes have a severe nature and be treatment-resistant. TNF-alpha, a cytokine associated with Th1, is known to play an important role in the pathogenesis of asthma. It is also known that TNF-alpha blocking agents have beneficial effects on the airway inflammation, lung histology, and asthma symptoms. Adalimumab (a human monoclonal anti-TNF alpha antibody) is a different TNF alpha blocking agent. In the present study, we have evaluated the effects of adalimumab (a human monoclonal anti-TNF alpha antibody) on the lung histology and lung inflammation in a murine model of asthma. The work presented in the current study shows that adalimumab treatment suppresses the airway inflammation, and provides improvement in histological findings in asthma. We may suggest that adalimumab is a promising alternative for the treatment of patients with severe asthma which is unresponsive to treatment.</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflicts of interest</span><p id="par0055" class="elsevierStylePara elsevierViewall">No competing financial interests exist and there is no conflicts of interest for each author.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Ethical disclosures</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Patients&#8217; data protection</span><p id="par0065" class="elsevierStylePara elsevierViewall">Confidentiality of Data. The authors declare that no patient data appear in this article.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Right to privacy and informed consent</span><p id="par0070" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article.</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Protection of human subjects and animals in research</span><p id="par0075" class="elsevierStylePara elsevierViewall">The authors declare that the procedures followed were in accordance with the regulations of the responsible Clinical Research Ethics Committee and in accordance with those of the World Medical Association and the Helsinki Declaration.</p></span></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">A few experimental studies related to asthma have unveiled the beneficial effects of TNF alpha blocking agents on the airway histology, cytokine levels in bronchoalveolar lavage and bronchial hyper-responsiveness. In the current study, we aimed to assess the effect of adalimumab on the inflammation and histology of asthma in a murine model.</p> <span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Twelve-week-old BALB/c (H-2d/d) female rats (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>18) were allocated into three groups, including (group I) control (phosphate-buffered saline was implemented), (group II) asthma induced with OVA (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6), and (group III) asthma induced with OVA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>treated with adalimumab (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6). Rats were executed on the 28th day of the study. The lung samples were fixed in 10% neutral buffered formalin. Lung parenchyma, alveolus, peribronchial and perivascular inflammation were assessed. Lung pathological scoring was performed.</p> <span class="elsevierStyleSectionTitle" id="sect0020">Result</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Severity of lung damage was found to be reduced significantly in the asthma induced with OVA<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>treated with adalimumab group. When compared with the untreated group, adalimumab significantly reduced the inflammatory cells around the bronchi and bronchioles, and reduced inflammation of the alveolar wall and alveolar wall thickness as well (median score<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>1, <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.52). Peribronchial smooth muscle hypertrophy and oedema were significantly reduced after adalimumab administration.</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Adalimumab (a human monoclonal anti-TNF alpha antibody) therapy significantly reduced the severity of lung damage by decreasing cellular infiltration and improvement on the lung histology in a murine model of acute asthma.</p>"
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">(1a and 1b) Normal alveoli and bronchi (control group), H&#38;E &times;40 and &times;100. (2a) Peri-bronchiolar and perivascular mix inflammation (asthma group), H&#38;E &times;40. (2b) Thickened alveolar walls with inflammation (asthma group), H&#38;E &times;100. (3a) The lung parenchyma without inflammation (adalimumab-treated group), H&#38;E &times;40. (3b) Mild thickened alveolar septa (adalimumab-treated group), H&#38;E &times;100.</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col">Area scored (number of cells)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="4" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Score</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Perivascular compartment<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No infiltration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;20 cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;100 cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#62;100 cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Bronchiolar epithelium&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No infiltration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;5 cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;10 cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#62;10 cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Peri-bronchiolar alveolar tissue<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No infiltration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;20 cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;100 cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#62;100 cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Alveolar walls<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No infiltration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#8211;3 cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#8211;5 cells&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#62;5 cells&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Group 1 &#38; Group 2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 (1&#8211;2) &#38; 4 (3&#8211;4)&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Group 1 &#38; Group 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1 (1&#8211;2) &#38; 1 (1&#8211;2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.523<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Group 2 &#38; Group 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4 (3&#8211;4) &#38; 1 (1&#8211;2)&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0.003<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0025"><span class="elsevierStyleItalic">p</span>: Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test.</p> <p class="elsevierStyleNotepara" id="npar0030">Group 1: Control group, Group 2: Murine asthma model, Group 3: Murine asthma model-adalimumab treated group.</p>"
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Comparison of the groups according to lung score.</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:24 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "(GINA) 2011. Available from: <a href="http://www.ginasthma.org/">http://www.ginasthma.org</a>"
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pathology of asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "J.C. Hogg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "1993"
                        "volumen" => "92"
                        "paginaInicial" => "1"
                        "paginaFinal" => "5"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8335845"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "TNF-alpha mediates recruitment of neutrophils and eosinophils during airway inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "N.W. Lukacs"
                            1 => "R.M. Strieter"
                            2 => "S.W. Chensue"
                            3 => "M. Widmer"
                            4 => "S.L. Kunkel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "1995"
                        "volumen" => "154"
                        "paginaInicial" => "5411"
                        "paginaFinal" => "5417"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7730642"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "TNF mediates lung leak, but not neutrophil accumulation, in lungs of rats given IL-1 intratracheally"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "B.M. Hybertson"
                            1 => "E.K. Jepson"
                            2 => "O.J. Cho"
                            3 => "J.H. Clarke"
                            4 => "Y.M. Lee"
                            5 => "J.E. Repine"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1164/ajrccm.155.6.9196104"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Crit Care Med"
                        "fecha" => "1997"
                        "volumen" => "155"
                        "paginaInicial" => "1972"
                        "paginaFinal" => "1976"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9196104"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Immunoregulatory activity of recombinant human tumor necrosis factor (TNF)-alpha: induction of TNF receptors on human T cells and TNFalpha-mediated enhancement of T cell responses"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "P. Scheurich"
                            1 => "B. Thoma"
                            2 => "U. Ucer"
                            3 => "K. Pfizenmaier"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "1987"
                        "volumen" => "138"
                        "paginaInicial" => "1786"
                        "paginaFinal" => "1790"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/3029221"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "TNF alpha is important in human lung allergic reactions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "T.B. Casale"
                            1 => "J.J. Costa"
                            2 => "S.J. Galli"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/ajrcmb.15.1.8679220"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "1996"
                        "volumen" => "15"
                        "paginaInicial" => "35"
                        "paginaFinal" => "44"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8679220"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tumour necrosis factor-alpha blockade suppresses murine allergic airways inflammation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S. Hutchison"
                            1 => "B.S. Choo-Kang"
                            2 => "R.V. Bundick"
                            3 => "A.J. Leishman"
                            4 => "J.M. Brewer"
                            5 => "I.B. McInnes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2249.2007.03509.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Immunol"
                        "fecha" => "2008"
                        "volumen" => "151"
                        "paginaInicial" => "114"
                        "paginaFinal" => "122"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17931392"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anti-tumor necrosis factor-alpha antibody treatment reduces pulmonary inflammation and methacholine hyper-responsiveness in a murine asthma model induced by house dust"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J. Kim"
                            1 => "L. McKinley"
                            2 => "S. Natarajan"
                            3 => "G.L. Bolgos"
                            4 => "J. Siddiqui"
                            5 => "S. Copeland"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/j.1365-2222.2005.02407.x"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Exp Allergy"
                        "fecha" => "2006"
                        "volumen" => "36"
                        "paginaInicial" => "122"
                        "paginaFinal" => "132"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16393274"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "FITC-induced murine pulmonary inflammation: CC10 up-regulation and concurrent Shh expression"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "C.E. Fisher"
                            1 => "S.A. Ahmad"
                            2 => "P.M. Fitch"
                            3 => "J.R. Lamb"
                            4 => "S.E. Howie"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.cellbi.2005.07.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Cell Biol Int"
                        "fecha" => "2005"
                        "volumen" => "29"
                        "paginaInicial" => "868"
                        "paginaFinal" => "876"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16150617"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Beta-arrestin-2 regulates the development of allergic asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J.K. Walker"
                            1 => "A.M. Fong"
                            2 => "B.L. Lawson"
                            3 => "J.D. Savov"
                            4 => "D.D. Patel"
                            5 => "D.A. Schwartz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI17265"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2003"
                        "volumen" => "112"
                        "paginaInicial" => "566"
                        "paginaFinal" => "574"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12925697"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Th1- and Th2-type cytokines regulate the expression and production of eotaxin and RANTES by human lung fibroblasts"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L.M. Teran"
                            1 => "M. Mochizuki"
                            2 => "J. Bartels"
                            3 => "E.L. Valencia"
                            4 => "T. Nakajima"
                            5 => "K. Hirai"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/ajrcmb.20.4.3508"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "1999"
                        "volumen" => "20"
                        "paginaInicial" => "777"
                        "paginaFinal" => "786"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10101011"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Human monocyte chemoattractant protein (MCP)-4 is a novel CC chemokine with activities on monocytes, eosinophils, and basophils induced in allergic and nonallergic inflammation that signals through the CC chemokine receptors (CCR)-2 and -3"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "E.A. Garcia-Zepeda"
                            1 => "C. Combadiere"
                            2 => "M.E. Rothenberg"
                            3 => "M.N. Sarafi"
                            4 => "F. Lavigne"
                            5 => "Q. Hamid"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Immunol"
                        "fecha" => "1996"
                        "volumen" => "157"
                        "paginaInicial" => "5613"
                        "paginaFinal" => "5626"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8955214"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the humanmast cell as a source of these cytokines"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P. Bradding"
                            1 => "J.A. Roberts"
                            2 => "K.M. Britten"
                            3 => "M.N. Sarafi"
                            4 => "F. Lavigne"
                            5 => "Q. Hamid"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/ajrcmb.10.5.8179909"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "1994"
                        "volumen" => "10"
                        "paginaInicial" => "471"
                        "paginaFinal" => "480"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8179909"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Human eosinophils release matrix metalloproteinase-9 on stimulation with TNF alpha"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "A. Schwingshackl"
                            1 => "M. Duszyk"
                            2 => "N. Brown"
                            3 => "R. Moqbel"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Allergy Clin Immunol"
                        "fecha" => "1999"
                        "volumen" => "104"
                        "paginaInicial" => "983"
                        "paginaFinal" => "989"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10550743"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Tumour necrosis factor (TNF alpha) as a novel therapeutic target in symptomatic corticosteroid dependent asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "P.H. Howarth"
                            1 => "K.S. Babu"
                            2 => "H.S. Arshad"
                            3 => "L. Lau"
                            4 => "M. Buckley"
                            5 => "W. McConnell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/thx.2005.045260"
                      "Revista" => array:6 [
                        "tituloSerie" => "Thorax"
                        "fecha" => "2005"
                        "volumen" => "60"
                        "paginaInicial" => "1012"
                        "paginaFinal" => "1018"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16166100"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Human antitumor necrosis factor monoclonal antibody (adalimumab) in Crohn&#39;s disease: the CLASSIC-I trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S.B. Hanauer"
                            1 => "W.J. Sandborn"
                            2 => "P. Rutgeerts"
                            3 => "R.N. Fedorak"
                            4 => "M. Lukas"
                            5 => "D. MacIntosh"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1053/j.gastro.2005.11.030"
                      "Revista" => array:6 [
                        "tituloSerie" => "Gastroenterology"
                        "fecha" => "2006"
                        "volumen" => "130"
                        "paginaInicial" => "323"
                        "paginaFinal" => "333"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16472588"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interleukin-10 inhibits antigen-induced cellular recruitment into the airways of sensitized mice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "C. Zuany-Amorim"
                            1 => "S. Haile"
                            2 => "D. Leduc"
                            3 => "C. Dumarey"
                            4 => "M. Huerre"
                            5 => "B.B. Vargaftig"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI117966"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "1995"
                        "volumen" => "95"
                        "paginaInicial" => "2644"
                        "paginaFinal" => "2651"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7769104"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Pharmacological evidence for tumor necrosis factor as a mediator of allergic inflammation in the airways"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L.M. Renzetti"
                            1 => "P.M. Paciorek"
                            2 => "S.A. Tannu"
                            3 => "C. Dumarey"
                            4 => "M. Huerre"
                            5 => "B.B. Vargaftig"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Pharmacol Exp Ther"
                        "fecha" => "1996"
                        "volumen" => "278"
                        "paginaInicial" => "847"
                        "paginaFinal" => "853"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8768739"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor alpha"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M.J. Elliott"
                            1 => "R.N. Maini"
                            2 => "M. Feldmann"
                            3 => "A. Long-Fox"
                            4 => "P. Charles"
                            5 => "P. Katsikis"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Arthritis Rheum"
                        "fecha" => "1993"
                        "volumen" => "36"
                        "paginaInicial" => "1681"
                        "paginaFinal" => "1690"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8250987"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Modulation of allergic inflammation in mice deficient in TNF receptors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "D.G. Rudmann"
                            1 => "M.W. Moore"
                            2 => "J.S. Tepper"
                            3 => "M.C. Aldrich"
                            4 => "J.W. Pfeiffer"
                            5 => "H. Hogenesch"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Am J Physiol-Lung Cell Mol Physiol"
                        "fecha" => "2000"
                        "volumen" => "279"
                        "paginaInicial" => "1047"
                        "paginaFinal" => "1057"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Development of airway hyperresponsiveness is dependent on interferon-gamma and independent of eosinophil infiltration"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E.M. Hessel"
                            1 => "A.J. Van Oosterhout"
                            2 => "I. Van Ark"
                            3 => "M.C. Aldrich"
                            4 => "J.W. Pfeiffer"
                            5 => "H. Hogenesch"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1165/ajrcmb.16.3.9070618"
                      "Revista" => array:6 [
                        "tituloSerie" => "Am J Respir Cell Mol Biol"
                        "fecha" => "1997"
                        "volumen" => "16"
                        "paginaInicial" => "325"
                        "paginaFinal" => "334"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9070618"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The soluble tumor necrosis factor-alpha receptor suppresses airway inflammation in a murine model of acute asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "H.S. Nam"
                            1 => "S.Y. Lee"
                            2 => "S.J. Kim"
                            3 => "J.S. Kim"
                            4 => "S.S. Kwon"
                            5 => "Y.K. Kim"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3349/ymj.2009.50.4.569"
                      "Revista" => array:6 [
                        "tituloSerie" => "Yonsei Med J"
                        "fecha" => "2009"
                        "volumen" => "50"
                        "paginaInicial" => "569"
                        "paginaFinal" => "575"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19718408"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anti-TNF alpha therapy is useful in rheumatoid arthritis and Crohn&#39;s disease: analysis of the mechanism of action predicts utility in other diseases"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M. Feldman"
                            1 => "P. Taylor"
                            2 => "E. Paleolog"
                            3 => "F.M. Brennan"
                            4 => "R.N. Maini"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Transplant Proc"
                        "fecha" => "1998"
                        "volumen" => "30"
                        "paginaInicial" => "4126"
                        "paginaFinal" => "4127"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9865320"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evidence of a role of tumor necrosis factor alpha in refractory asthma"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M.A. Berry"
                            1 => "B. Hargadon"
                            2 => "M. Shelley"
                            3 => "D. Parker"
                            4 => "D.E. Shaw"
                            5 => "R.H. Green"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa050580"
                      "Revista" => array:6 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2006"
                        "volumen" => "354"
                        "paginaInicial" => "697"
                        "paginaFinal" => "708"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16481637"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
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        "texto" => "<p id="par0080" class="elsevierStylePara elsevierViewall">The authors thank Tuncay Delibas¿, M.D., and the Ankara D¿¿kap¿ Hospital, Research Center, Animals Research Laboratory&#39;s workers for providing help in nursing, immunisation with OVA and sacrificing of animals.</p>"
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Article information

ISSN: 03010546
Original language: English

DOI:10.1016/j.aller.2013.11.002

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Year/Month	Html	Pdf	Total

2024 November	4	1	5
2024 October	36	11	47
2024 September	44	11	55
2024 August	51	7	58
2024 July	38	8	46
2024 June	34	12	46
2024 May	35	8	43
2024 April	42	8	50
2024 March	40	4	44
2024 February	27	7	34
2024 January	405	4	409
2023 December	19	15	34
2023 November	17	12	29
2023 October	32	10	42
2023 September	16	3	19
2023 August	29	8	37
2023 July	30	24	54
2023 June	30	2	32
2023 May	50	9	59
2023 April	47	2	49
2023 March	23	8	31
2023 February	15	9	24
2023 January	14	17	31
2022 December	24	8	32
2022 November	22	11	33
2022 October	23	17	40
2022 September	23	18	41
2022 August	45	15	60
2022 July	32	5	37
2022 June	33	13	46
2022 May	40	12	52
2022 April	64	16	80
2022 March	102	27	129
2022 February	106	8	114
2022 January	69	5	74
2021 December	74	8	82
2021 November	56	8	64
2021 October	43	11	54
2021 September	31	10	41
2021 August	46	6	52
2021 July	14	7	21
2021 June	17	10	27
2021 May	32	8	40
2021 April	63	18	81
2021 March	21	14	35
2021 February	13	19	32
2021 January	10	2	12
2020 November	0	1	1
2020 September	0	2	2
2020 August	0	1	1
2020 July	0	1	1
2020 May	0	2	2
2020 April	0	3	3
2020 March	0	3	3
2020 February	0	6	6
2020 January	0	1	1
2019 December	0	1	1
2019 November	0	2	2
2019 October	0	2	2
2019 August	0	3	3
2019 July	0	7	7
2019 June	0	1	1
2019 May	0	10	10
2019 April	0	6	6
2019 March	0	2	2
2019 February	0	3	3
2018 March	4	0	4
2018 February	14	6	20
2018 January	15	2	17
2017 December	24	4	28
2017 November	13	5	18
2017 October	22	5	27
2017 September	8	10	18
2017 August	23	13	36
2017 July	18	7	25
2017 June	30	28	58
2017 May	31	18	49
2017 April	34	14	48
2017 March	20	22	42
2017 February	25	3	28
2017 January	15	9	24
2016 December	34	5	39
2016 November	40	6	46
2016 October	41	12	53
2016 September	43	6	49
2016 August	39	4	43
2016 July	32	6	38
2016 June	31	12	43
2016 May	18	9	27
2016 April	35	16	51
2016 March	35	14	49
2016 February	29	13	42
2016 January	21	14	35
2015 October	0	1	1
2015 May	0	1	1
2015 April	1	6	7
2015 March	1	2	3
2015 February	3	8	11

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