Interferons in the pathogenesis and treatment of human immunodeficiency virus infection.
There still remains several unanswered questions concerning the pathogenesis of human immunodeficiency virus (HIV) infection. Interferons (IFNs), as well as other cytokines, are both dysregulated in HIV infection and serve as effector molecules that modulate the replicative capacity of HIV. Acid-labile IFN-alpha, an aberrant form of interferon earlier described in certain autoimmune diseases, has been detected in HIV-infected individuals. Conversely, a deficient expression of IFN-alpha may occur usually associated with HIV disease. Although conflicting findings have been reported on whether IFN-gamma, a product of activated T and natural killer (NK) cells, is elevated in the peripheral blood (PB) compartment, high levels of its expression have been observed in the germinal centers of the lymph nodes during HIV disease. IFN-alpha and IFN-beta have shown potent anti-retroviral effects in several in vitro systems of both acute and chronic HIV infection. These findings have served as the basis of the rationale for their therapeutic application, resulting in some positive effects at least in those patients with relatively high CD4+ T cell counts and healthy immune functions. Furthermore, IFN-alpha has shown important therapeutic effects on HIV-associated Kaposi's sarcoma (KS). Both suppressive and inductive effects on HIV replication in vitro have been described for IFN-gamma, whereas no clear clinical benefits have been reported following its administration to HIV-infected individuals. In conclusion, IFNs are involved in several pathogenic aspects of HIV infection and AIDS, and certain IFNs may serve as important tools to limit the spread of the virus and the progression of disease.
Poli
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AIDS Immunopathogenesis Unit, DIBIT, San Raffaele Scientific Institute, Milano, Italy.
Biswas
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P
Fauci
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AS
D006678:HIV / Q000187:drug effects* / Q000254:growth & development; D015658:HIV Infections / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000378:metabolism / Q000627:therapeutic use*; D014779:Virus Replication / Q000187:drug effects
D007372:Interferons