Ribavirin enhancement of hepatitis C virus core antigen-specific type 1 T helper cell response correlates with the increased IL-12 level

Abstract

Backgrounds/Aims: Combination IFN-α and ribavirin therapy for hepatitis C virus-infected patients has been reported to improve the response rate up to 50%. In this study, we aimed to study further the role of ribavirin in hepatitis C virus-specific immune responses. Methods: We immunized mice with hepatitis C virus core protein with or without different concentrations of ribavirin. Forty days after immunization, hepatitis C virus-specific immune responses were followed in these mice. Results: We found that the mice immunized with core antigen once every 2 weeks and 0.5 mg ribavirin every day showed higher levels of core-specific IgG2 compared with those mice immunized with core antigen only. In addition, core antigen-stimulated spleen cells produced higher levels of T helper type 1 cytokines and the core-specific cytotoxic T cell activity also increased significantly. Furthermore, lipopolysaccharide-stimulated peritoneal cells produced higher levels of IL-12 in ribavirin-treated mice, and peritoneal cells isolated from naïve mice also produced significantly higher level of IL-12 when cultured with ribavirin. Conclusions: Ribavirin may significantly promote the T helper type 1 immune response in vivo, and, furthermore, the effect of ribavirin on IL-12 level produced by accessory cells may contribute to the T helper type 1 enhancing effect.