Article information
Resumen
Las estatinas son fármacos hipolipemiantes usados para controlar la aterogénesis y las enfermedades cardiovasculares originadas por hipercolesterolemia. Recientemente, se describieron varios efectos pleótropos de las estatinas, dependientes e independientes de la inhibición de la síntesis del colesterol, que van desde la regulación de la respuesta inmunitaria hasta la inhibición de la infección y la replicación viral. El tratamiento antirretroviral contra el VIH inhibe su replicación en las células infectadas, disminuyendo hasta niveles indetectables las copias del ARN viral en el plasma. Esto se asocia al incremento de los linfocitos T CD4+ circulantes y la disminución en la incidencia de infecciones oportunistas y en la mortalidad. Sin embargo, el costo y la complejidad del esquema antirretroviral, además de los efectos colaterales y la aparición de cepas resistentes, indican la necesidad de nuevos tratamientos para la infección por VIH. Como el VIH requiere del colesterol y las balsas de lípidos de la membrana celular para infectar las células blanco y cumplir su ciclo de replicación, se postula que las estatinas pueden ser una alternativa efectiva para ayudar al control de esta infección. La actividad anti-VIH de las estatinas no va dirigida contra las proteínas virales, muy variables por la mutabilidad del virus, sino que se centra en las células afectadas, bloqueando la infección por VIH y modulando su respuesta funcional; desde esta perspectiva, las estatinas evitarían la resistencia por mutaciones virales e intervendrían modulando la respuesta inmunitaria ampliamente alterada por el VIH.
Palabras clave:
estatinas
inmunomodulación
actividad antiviral
virus de inmunodeficiencia humana.
Abstract
Statins are hypolipemiant drugs used for controlling atherogenesis and cardiovascular diseases caused by hypercholesterolemia. Recently, several pleiotropic effects of statins have been reported, whereas dependent or independent of downregulating cholesterol synthesis; these effects range from immune response modulation to inhibition of the infection and viral replication. The antiretroviral therapy against HIV inhibits viral replication in infected cells, decreasing to undetectable levels the number of viral RNA copies in plasma. Consequently, there is an increase in circulating CD4+ T-cell count, and a decrease in the incidence of opportunistic infections and mortality. However, the cost and complexity of antiretroviral regimens, the frequent side effects and the emergence of resistant strains, indicate the need of new approaches for HIV infection. Since HIV virions require of cholesterol in their envelope and the integrity of host membrane lipid rafts, in order to infect target cells and to perform several steps of their replication cycle, it has been proposed that the use of statins in HIV-1 infected patients can be an effective alternative to help control this infection. The anti-HIV activity of statins is not directed against viral proteins, which are highly variable due to viral mutations, but instead it focuses on cellular targets blocking their infection and regulating their functional responses. From this point of view, statins could avoid the emergence of resistant viral strains and intervene in the modulation of the highly altered immune responses.
Keywords:
Statins
immunomodulation
antiviral activity
human immunodeficiency virus.
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