HIV‐1 Inhibits Leishmania‐lnduced Cell Proliferation but not Production of Interleukin‐6 and Tumour Necrosis Factor Alpha

The immune response of normal human peripheral blood mononuclear cells (PBMC) after stimulation with human immunodeficiency virus-1 (HIV-1) antigens plus Leishmania donovani promastigotes in vitro was investigated. HIV-1-antigen stimulation of PBMC did not induce the intracellular accumulation of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), or interferon-gamma (IFN-gamma). However, cells stimulated with L. donovani antigens exhibited the production of IL-6 and TNF-alpha, but not IFN-gamma. Furthermore, co-stimulation of PBMC with HIV-1 antigen plus L. donovani resulted in the intracellular accumulation of IL-6 and TNF-alpha comparable to that of cells that were activated with L. donovani antigen alone. Heat-inactivated HIV-1 antigen did not appear to induce or suppress cytokine production by PBMC. However, the same HIV antigens did suppress L. donovani-induced proliferation as well as PPD-induced proliferation in a dose-dependent fashion. Elevated levels of serum cytokines have been demonstrated in patients with HIV infection indicating their role in the pathogenesis of HIV-associated immunosuppression. The results may partially support the idea that the abnormally increased cytokine levels in the sera of HIV-infected subjects is due to the various opportunistic pathogens that these patients contract, rather than a response to HIV antigens. As cytokines have been shown to up-regulate HIV replication, the data suggest a role for opportunistic infections in cytokine-induced transactivation of HIV-1 and disease progression.