Therefore, interferon gamma (IFN-gamma) production by peripheral blood mononuclear cells (PBMC) derived from patients with chronic HCV infection (genotype 1b) was examined.
These data thus demonstrate a close association between the amount of IFN-gamma transcripts in PBMC and in liver tissue and the inflammatory activity in chronic HCV infection in man.
The presented data are compatible with the assumption that HCV might be able to stimulate iNOS expression both directly and indirectly via its capacity to induce IFN-gamma.
As cell immunity seems to be involved in chronic hepatitis C virus (HCV), study of the events regulated by IFN-gamma may be useful in evaluating the host's immunological response.
The significant upregulation of IFNgamma and IL-18 mRNA and significant correlations between IFNgamma and other proinflammatory cytokines, suggest a Th1/cell mediated intrahepatic immune response in chronic HCV infection.
Furthermore, a genetic tendency to produce higher levels of IFN-gamma was noted among LTx recipients with nonrecurrent hepatitis C than among those with recurrent hepatitis C.
Liver TCRgammadelta(+) T-cell lines from HCV-infected individuals had high levels of non-major histocompatibility complex (MHC)-restricted cytotoxic activity against different targets including primary hepatocytes and produced interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and interleukin 8 (IL-8) following activation by anti-CD3.
Interferon-gamma-inducible protein 10 (IP-10), a chemokine that recruits activated T lymphocytes, has recently been shown by in situ hybridization to be expressed in the liver during chronic HCV infection.
Interferon-gamma mRNA was increased in both haemochromatosis (0.29+/-0.08%, P=0.01) and hepatitis C patients (1.02+/-0.32%, P=0.03) compared to controls (0.04+/-0.01%).
Interestingly, most HCV-specific CD4 T-cell proliferative responses in AA patients were unaccompanied by concurrent interferon gamma (IFN-gamma) production, suggesting a dysregulated virus-specific, CD4 T-cell effector function during chronic HCV infection.
As compared with controls, we found major changes in T-lymphocyte subsets in HCV-infected patients, with a significant decrease of T-cell antigen receptor (TCR) delta and CD56 gene expression, associated with a concomitant increase of TCRalpha and CD8beta that were correlated with cytotoxic factors, proinflammatory chemokines, and chemokine receptors including peforin, interferon gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), RANTES, and CXCR3.
To investigate the intra-hepatic activation of the IFN system in patients affected by chronic HCV-infection in comparison with that observed in a non-infectious liver disease such as non-alcoholic steatohepatitis, we measured the liver steady state mRNA levels of interferon-alpha, interferon-beta and interferon-gamma as well as of IFN-related genes (IFNAR-1, STAT1alpha, PKR, 2-5 AS, IRF-1, ICE and IL-18).
Ex vivo interferon gamma (IFN-gamma) ELISPOT analysis detected HCV-specific CD4(+) T-helper cell reactivity in only 35% of cases, whereas HCV-specific CD8(+) T-cell responses were found in 4 of 5 HLA-A2-positive individuals.
Interferon-gamma (IFN gamma)-producing CD8+ T cells have been shown to play a key role in the control or eradication of hepatitis C virus (HCV) infections.
In 116 consecutive patients with CH-C, we tested the hypothesis that host genetic factors regulating IFN-gamma production and activity influence the severity of liver damage and hepatitis C virus (HCV)-specific T-cell reactivity.
Given that the complications of hepatitis C are due to fibrosis, we hypothesized that the antifibrotic effects of interferon gamma on stellate cells would lead to beneficial effects in patients with hepatitis C. Thus, we evaluated the safety and efficacy of interferon gamma-1b in patients with hepatitis C. A cohort of 20 patients with chronic hepatitis C who failed or were intolerant to previous interferon-alpha-based regimens received 200 mug of interferon gamma-1b subcutaneously three times weekly for 24 weeks.
Preservation of HCV-specific LP responses in coinfected individuals was associated with a higher nadir CD4 count (r(2) = 0.45, p < 0.001) and the presence and magnitude of the HCV-specific CD8(+) T cell interferon-gamma response (p = 0.0014).