We have previously demonstrated that cytokines play a major role in the pathogenesis of HIV disease both in the modulation of HIV expression and in the immunologic abnormalities noted in HIV-infected individuals. We have investigated the constitutive expression of a panel of cytokines including interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma in peripheral blood (PB) and lymph nodes (LN) from human immunodeficiency virus type 1 (HIV-1)- infected individuals during different stages of disease. Constitutive expression of IL-1beta, IL-10, IFN-gamma, and TNF-alpha in PB and LN is significantly higher in HIV-infected individuals compared to HIV-negative individuals. Levels of IL-6 increase in PB with disease progression and levels of IL-2 and IL-4 are low to absent at any stage of disease. Longitudinal analysis of constitutive cytokine expression in PB of HIV- infected individuals at different stages of disease has been unable to demonstrate changes in the pattern of cytokine expression associated with disease progression. Constitutive cytokine expression in sorted CD4+ and CD8+ T lymphocytes has shown that CD4+ T cells express very low levels of cytokines at any stage of infection. CD8+ T cells are involved in the constitutive expression of IFN-gamma, and to a lesser extent of IL-10. Stimulation in vitro of purified CD4+ T cells from patients during different stages of disease has not demonstrated any change in the pattern of cytokine expression associated with disease progression. Longitudinal analysis of constitutive cytokine expression in PB from HIV- infected individuals following primary infection has shown that levels of IL-2, IL-4, and IL-6 are low to absent in PB as early as the period of primary infection. In contrast, high levels of constitutive expression of IL-10, IFN-gamma, and TNF-alpha are associated with primary HIV infection.
