Cytokines and cytokine therapies in HIV infection.

HIV infection is characterized by a variety of disturbances in the regulation of cytokine expression. These disturbances include a general decrease in the expression of type 1 T-helper cytokines, an increase in expression of proinflammatory cytokines, a possible increase in type 2 helper cytokines, and increased expression of antiviral interferons and TGF-beta. These perturbations may contribute to HIV disease pathogenesis by contributing to the impaired cellular immune responses and cell loss that characterize HIV infection and AIDS and by accelerating replication of HIV-1. Treatment trials utilizing cytokines and their inhibitors may provide useful adjuncts in the management of HIV-1 disease, and at the same time they can be designed to help clarify the role of cytokine dysregulation in the pathogenesis of HIV-1 disease. Although powerful combinations of antiretroviral drugs can reduce plasma HIV levels below the limits of detection, it is not clear that full immunological reconstitution is a consequence of these interventions. Trials of immune-based therapies, including trials of cytokines and their inhibitors, are therefore an increasingly important component of our treatment research agenda.