THE ANTIVIRAL COMPOUND RIBAVIRIN MODULATES THE T-HELPER (TH)1 TH2 SUBSET BALANCE IN HEPATITIS-B AND HEPATITIS-C VIRUS-SPECIFIC IMMUNE-RESPONSES/

Ribavirin is effective in combination therapies against chronic hepati tis C virus (HCV) infection, although its direct antiviral properties are unclear, We therefore studied the immune-modulatory effects of rib avirin on hepatitis B virus (HBV)- and HCV-specific immune responses. During a 24 week placebo-controlled ribavirin trial in ten patients wi th chronic HCV infection, HCV antibodies and alanine aminotransferase (ALT) levels decreased transiently whereas the serum levels of HCV RNA remained stable. Effects of ribavirin on human and murine phytohaemag glutinin (PHA)-activated T cells included inhibition of in vitro proli feration and modulation of IL-2, IL-4, IFN-gamma, and TNF-alpha levels . HBcAg- and HBeAg-specific IL-2 and IFN-gamma levels were greater tha n or equal to 25-fold higher in mice immunized with HBV core- or e-ant igens (HBcAg, HBeAg) while receiving ribavirin compared to untreated m ice, but IL-4 and IL-6 remained constant. Concordantly, a slight shift was observed in the IgG subclass distribution of the humoral response s of ribavirin-treated mice to HBeAg and HCV NS3 protein, Ribavirin tr eatment of HBeAg-transgenic (HBeAg-Tg) mice induced a dose-dependent d own-regulation of T helper (Th)2-mediated antibody production to HBeAg , In ribavirin-treated HBeAg-Tg mice anti-HBe IgG1 (positively regulat ed by Th2 cytokines) decreased simultaneously as both anti-HBe IgG2a ( positively regulated by Th1 cytokines) levels and in vitro T-cell IFN- gamma production increased, indicating a change in the Th1/Th2 balance . Thus, the present data suggest that ribavirin is not strictly an ant iviral compound, but rather it alters the T-cell balance in the immune system.