INTERFERON GAMMA-TREATMENT BUT NOT ALPHA-TREATMENT PREVENTS FIBROSIS BY INHIBITING PROCOLLAGEN AND TISSUE INHIBITOR OF METALLOPROTEINASE-1 GENE-EXPRESSION IN PIG SERUM-INDUCED RAT-LIVER FIBROSIS IN-VIVO

The aim of this study was to investigate the effect of interferons-gam ma (IFN-gamma) and -alpha (IFN-alpha) on the synthesis of matrix prote ins such as collagens as well as the gene expression of tissue inhibit or of metalloproteinase-1 (TIMP-1) in vivo. We investigated the effect s of IFN-gamma and -alpha in a model of liver fibrosis induced by pig serum in male Wistar rats, which develop fibrosis without an increase in serum ALT (i.e. without hepatocyte injury). Rats were injected with 0.5 ml of pig serum twice a week for 8 weeks with or without 50000 U of IFN-gamma or 100000 U of IFN-alpha. IFN-gamma at the dose of 50000 U day(-1) prevented fibrosis, as indicated by reduced hydroxyproline c ontent in the liver. IFN-gamma at 50000 U day(-1) also reduced express ion of type I procollagen as well as TIMP-1 in the liver. However, fib rosis was nor reduced by IFN-alpha. Histologically, IFN-gamma at 50000 U day(-1) also reduced the number of myofibroblast-like cells (activa ted stellate cells). These results indicate that IFN-gamma, but not IF N-alpha, can prevent fibrosis by inhibiting the activation and prolife ration of stellate cells, resulting in reduced expression of procollag en and TIMP-1 mRNA in pig serum-induced rat liver fibrosis in vivo. (C ) 1998 Elsevier Science Ireland Ltd. All rights reserved.