Cytokine gene expression in cirrhotic and non-cirrhotic human liver

Background/Aims: In order to explore the role of cytokines in the pathogenesis of liver cirrhosis, we analyzed their gene expression in hepatic biopsies from patients with alcoholic liver cirrhosis, post-hepatitis C liver cirrhosis, and with idiopathic portal hypertension without cirrhosis. Methods: We assessed the gene expression of interleukins 1β, 2, 6, 8, and 10, as well as of tumor necrosis factor-α, transforming growth factor-β and interferon-γ by a quantitative polymerase chain reaction. Results: We found high levels of transforming growth factor-β in post-hepatitis C liver cirrhosis, high to moderate in alcoholic liver cirrhosis and low in non-cirrhotic specimens. Expression of interleukin-10, tumor necrosis factor-α, and interferon-γ genes was detected in most post-hepatitis C liver cirrhosis, but not in idiopathic portal hypertension or alcoholic liver cirrhosis biopsies. The interleukin1-β, 6 and 8 gene expression was significantly lower in alcoholic liver cirrhosis compared to post-hepatitis C liver cirrhosis, but higher compared to idiopathic portal hypertension specimens. Thus, post-hepatitis C liver cirrhosis samples showed a high degree of cytokine gene expression, whereas in alcoholic liver cirrhosis it tended to be moderate, and restricted to some cytokines (transforming growth factor-β, interleukin-1, 6 and 8, but not interleukin-10, tumor necrosis factor-α or interferon-γ). In contrast, most non-cirrhotic specimens showed a restricted and low cytokine gene expression. Conclusions: These data suggest that transforming growth factor-β may have an important role in liver fibrosis and inflammation. Interleukin-1β, 6, 8, tumor necrosis factor-α and interferon-γ, appear to participate in the pathogenesis of the mild to severe inflammatory phenomena seen in alcoholic and post-hepatitis C liver cirrhosis, respectively. Our data suggest that tumor necrosis factor-α does not participate in the hepatocellular damage of alcoholic liver cirrhosis, and indicate that neither interferon-γ nor interleukin-10, at least at the levels observed in post-hepatitis C liver cirrhosis, are able to counteract the fibrotic/inflammatory process seen in this condition.