HIV-1 alters T helper cytokines, interleukin-12 and interleukin-18 responses to the protozoan parasite Leishmania donovani

Objective: To investigate the in vitro and in vivo effect of HIV-1 on lymphoproliferative and T helper (Th) cytokine responses in leishmaniasis. Methods: Th1 [interleukin (IL)-2 and interferon (IFN)-gamma] and Th2 (IL-4 and IL-10) as well as IFN-gamma-inducing cytokines (IL-12 and IL-18) were measured in antigen and mitogen-stimulated culture supernatants of peripheral blood mononuclear cells (PBMC) of healthy donors, HIV-infected and visceral leishmaniasis (VL) patients with or without HIV co-infection. Results: Proliferative responses to phytohaemagglutinin (PHA) were significantly lower in PBMC from VL and asymptomatic HIV-infected persons compared with responses in healthy individuals. VL-HIV co-infected patients showed the lowest responses. Although there was no significant difference in the Leishmania-induced proliferative responses among the healthy group and those infected with HIV only, VL patients (with or without HIV) exhibited very low proliferation. When cultured with PHA or Leishmania, PBMC from healthy donors produced high levels of a Th1 cytokine (IFN-gamma) and low levels of Th2 cytokines (IL-4 and IL-10). In addition, coculturing PBMC from healthy donors with a killed HIV preparation abrogated the production of IFN-gamma induced by Leishmania and augmented IL-4 and IL-10 production. Cells from HIV-infected patients produced low levels of IFN-gamma, but high levels of IL-10. The addition of anti-IL-10 did not increase Leishmania-induced proliferative responses or IFN-gamma production, Both IL-12 and/or IL-18 responses were lower in VL patients, HIV-infected, or VL-HIV co-infected patients as compared with those of healthy donors. Conclusion: The data suggest that the inhibitory effect of HIV and VL on proliferation and lFN-gamma production is not due to IL-10 alone, but that the defect induced by HIV and VL probably operates at the level of regulation of IFN-gamma-inducing factors, such as Introduction IL-12 and IL-18. (C) 2000 Lippincott Williams & Wilkins.