Treatment with ribavirin and interferon-alpha reduces interferon-gamma expression in patients with chronic hepatitis C

Recent studies in vitro and in animals have suggested that ribavirin may po tentiate the antihepatitis C virus (HCV) activity of interferon-alpha (IFN- alpha) by up-modulating the production of T cell-derived cytokines, such as interleukin (IL)-2 and IFN-gamma, which play a key role in the cellular im mune response against HCV. To study the immune-modulatory mechanisms of rib avirin further, cytokine production by activated T cells and circulating cy tokine levels were studied by FACS analysis and ELISA testing in 25 patient s with chronic hepatitis C unresponsive to IFN-alpha, before and after trea tment with either ribavirin plus IFN-alpha or IFN-alpha alone. After 16 wee ks of treatment, both the expression of IFN-gamma by activated T cells and the blood levels of IFN-gamma, were significantly reduced with respect to p retreatment values in patients treated with ribavirin and IFN-alpha but not in those undergoing treatment with IFN-alpha alone. The expression of IFN- gamma was significantly lower in patients that gained normal ALT levels wit h respect to those that did not. No modification of the expression of IL-2, IL-4 and IL-10 was found before and after treatment in either group of pat ients. In conclusion, the results of this study do not support up-modulatio n of IFN-gamma and IL-2 production as the mechanism by which ribavirin pote ntiates IFN-alpha anti HCV activity. In addition, our findings suggest that ribavirin may exert an anti-inflammatory effect and may help reducing IFN- gamma -driven T cell activation and liver damage.