Cytokine gene expression in cirrhotic and non-cirrhotic human liver

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.

We assessed the gene expression of interleukins 1 beta, 2, 6, 8, and 10, as well as of tumor necrosis factor-alpha, transforming growth factor-beta and interferon-gamma by a quantitative polymerase chain reaction.

We found high levels of transforming growth factor-beta 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-alpha, and interferon-gamma genes was detected in most post-hepatitis C liver cirrhosis, but not in idiopathic portal hypertension or alcoholic liver cirrhosis biopsies. The interleukin1-beta, 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-beta, interleukin-1, 6 and 8, but not interleukin-10, tumor necrosis factor-alpha or interferon-gamma). In contrast, most non-cirrhotic specimens showed a restricted and low cytokine gene expression.

These data suggest that transforming growth factor-beta may have an important role in liver fibrosis and inflammation. Interleukin-1 beta, 6, 8, tumor necrosis factor-alpha and interferon-gamma, 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-alpha does not participate in the hepatocellular damage of alcoholic liver cirrhosis, and indicate that neither interferon-gamma 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.