The study of mononuclear cell responses after humanrnimmunodeficiency virus type-l (HIV-l ) activation may help inrnproviding some insight into the understanding of the pathogenicrnmechanisms of HIV infection or acquired immunodeficiency syndromern(AIDS)-related disorders. The secretion of three cytokines,rninterleukin-6 (IL-6) , tumor necrosis factor (TNF)-alpha, andrninterferon(IFN)-gamma by peripheral blood mononuclear cells(PBMC)rnwas determined after in vitro stimulation with heat -inactivatedrnHIV-I antigens, using cytokine-specific monoclonal antibodies andrnan indirect immunofluorescence technique. HIV-l antigenrnstimulation of PBMC from healthy donors did not induce thernintracellular accumulation of IL-6, TNF-alpha, or IFN-gamma.rnSimilarly, cells from asymptomatic HIV-infected subjects did notrnresult in cytokine production either spontaneously or f ollowingrnstimulation with HIV antigen. After activation with mitogen o rrnantigen,cells from HIV-infected persons produced amounts of IL-6,rnTNF-alpha and IFN-gamma comparable to that of cells from healthyrnindividuals. Furthermore, co-st imulation o f normal PBMC with HIVantigenrnplus L.donovani resulted in intracellular accumulationrnof IL-6 and TNF-alpha comparab~ e to that of cells that werernactivated with Leishmania antigen alone. Heat-inactivated HIV-lrnantigen does n o t appear to induce or modulate cytokine productionrnby PBMC. A defect in cytokine production is also accompanied byrni nh ibition of PPD-induced lymphoproliferative responses . Elevatedrnlevels o f serum cytokines have been demonstrated in patients withrnHIV infection indicating their role in the pathogenesis ofrnHIV-associated infections. Theref ore, data from our results mayrnpartly support the idea that t he cause o f the abnormal l yrnincreased cycokine levels in t he sera o f HIV-infected subjectsrnxrnmight be jue to a variety of opportunistic pathogens that thesernpatients contract. As cytokines have been shown t o up-regulaternHIV repl ication, our data addit i onally demonstrate a role f o rrnopportunistic infections in cytokine induced transactivation ofrnHIV-l and disease progression.