HETEROGENEITY OF CYTOKINE FUNCTIONS IN HIV-INFECTION

Immunological responses, especially cytokines, play important roles in determining the persistence of infectious agents in chronic diseases, Th1 responses enhance cellular immunity to control infection whereas Th2 immune responses down-regulate these effector immune responses, It has been suggested that the Th1 to Th2 snitch is involved in human im munodeficiency virus (HIV) disease progression. We studied the regulat ory role of interleukin-4 (IL-4: Th2 response on interferon-gamma (IFN -gamma; Th1 response) in HIV infection and its role in the generation of HIV-specific cytotoxic T lymphocytes (CTL in an irt vitro system. F orty HIV-infected, asymptomatic individuals and 20 HIV-seronegative in dividuals were included in this study, Peripheral blood mononuclear ce lls were stimulated with phytohaemagglutinin and tetanus toroid in the presence or absence of IL-4 to determine the effect of IL-4 on IFN-ga mma production and HIV-Env-specific CTL activity, IL-4 showed a dual e ffect on IFN-gamma production in HIV patients. IL-4 down-regulated IFN -gamma production in HIV-seronegative individuals and in 55% of HIV pa tients whereas it stimulated IFN-gamma production in 45% of HIV patien ts. IL-4 increased HIV-Env-specific CTL activity in ave of seven patie nts of the latter group. IL-4 has multiple biological activities, e.g. , IL-4 inhibits IFN-gamma production as well as stimulates CTL generat ion which in turn produces IFN-gamma, Understanding the biological sig nificance of these interactions is of importance for immunotherapeutic approaches against HIV infection.