Liver infiltrating T lymphocytes express interferon gamma and inducible nitric oxide synthase in chronic hepatitis C virus infection

Background-Pathogenesis of hepatitis C virus (HCV) associated Liver injury is thought to be due to the host antiviral immune response. Using a quantit ative, competitive RT-PCR technique, we recently showed that expression of interferon gamma (IFN-gamma) and IFN-gamma inducible type of nitric oxide s ynthase (iNOS) is increased in homogenised liver tissue of patients with ch ronic HCV infection. Aims--To determine the cellular origin of IFN-gamma and iNOS expression and to examine the hypothesis that T cell derived IFN-gamma secretion induces iNOS in hepatocytes in chronic HCV infection. Methods--By applying a non-radioactive in situ hybridisation method combine d with indirect immunofluorescence, 33 liver biopsy specimens from patients with chronic HCV infection were studied for cellular expression of IFN-gam ma and iNOS mRNA. Results--In chronic HCV infection, both IFN-gamma and iNOS gene expression were significantly increased. IFN-gamma and iNOS mRNA were observed in CD3 lymphocytes infiltrating portal tracts and hepatic lobules, but not in hep atocytes. Conclusions-Results are consistent with previous reports that IFN-gamma and iNOS transcripts are elevated in chronic HCV infection. In contrast to the hypothesis, IFN-gamma expressing T cells do not induce iNOS in hepatocytes , but probably in T cells. T lymphocytes expressing IFN-gamma and/or iNOS h ave the potential to participate in autocrine and paracrine pathways that m ay contribute to the pathobiology of chronic hepatitis C.