Interferon gamma treatment prevents procollagen gene expression without affecting transforming growth factor-β1 expression in pig serum-induced rat liver fibrosis in vivo

Background/Aim: The aim of this study was to investigate the effect of interferon gamma on the synthesis of matrix proteins such as collagens with the relation to transforming growth factor-β1 expression in vivo. Methods: We investigated the effects of interferon gamma in a model of liver fibrosis induced by pig serum in male Wistar rats, which develops fibrosis without an increase in serum alanine aminotransferase (i.e., without hepatocyte injury). Rats were injected with 0.5 ml of pig serum twice a week for 8 weeks with or without 20 000 or 50 000 U of interferon gamma. Results: Interferon gamma at doses up to 50 000 U/day prevented fibrosis, as indicated by reduced hydroxyproline content in the liver. Interferon gamma at 50 000 U/day also reduced expression of type I and III procollagen in the liver. However, the expression of transforming growth factor-β1 mRNA and protein in the liver was not reduced by interferon gamma. Histologically, interferon gamma at 50 000 U/day also reduced the number of myofibroblast-like cells (activated stellate cells). Conclusions: These results indicate that interferon gamma can prevent fibrosis by inhibiting the activation and proliferation of stellate cells, resulting in reduced expression of procollagen without affecting transforming growth factor-β1 expression in pig serum-induced rat liver fibrosis in vivo.