Treatment with ribavirin and interferon-α reduces interferon-γ expression in patients with chronic hepatitis C

Abstract

Summary Recent studies in vitro and in animals have suggested that ribavirin may potentiate the antihepatitis C virus (HCV) activity of interferon-α (IFN-α) by up-modulating the production of T cell-derived cytokines, such as interleukin (IL)-2 and IFN-γ, which play a key role in the cellular immune response against HCV. To study the immune-modulatory mechanisms of ribavirin further, cytokine production by activated T cells and circulating cytokine levels were studied by FACS analysis and ELISA testing in 25 patients with chronic hepatitis C unresponsive to IFN-α, before and after treatment with either ribavirin plus IFN-α or IFN-α alone. After 16 weeks of treatment, both the expression of IFN-γ by activated T cells and the blood levels of IFN-γ, were significantly reduced with respect to pretreatment values in patients treated with ribavirin and IFN-α but not in those undergoing treatment with IFN-α alone. The expression of IFN-γ was significantly lower in patients that gained normal ALT levels with 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 patients. In conclusion, the results of this study do not support up-modulation of IFN-γ and IL-2 production as the mechanism by which ribavirin potentiates IFN-α anti HCV activity. In addition, our findings suggest that ribavirin may exert an anti-inflammatory effect and may help reducing IFN-γ-driven T cell activation and liver damage.