CYTOKINE GENE-EXPRESSION IN CIRRHOTIC AND NONCIRRHOTIC HUMAN LIVER

Background/Aims: In order to explore the role of cytokines in the path ogenesis of liver cirrhosis, we analyzed their gene expression in hepa tic biopsies from patients with alcoholic liver cirrhosis, post-hepati tis C liver cirrhosis, and with idiopathic portal hypertension without cirrhosis. Methods: We assessed the gene expression of interleukins 1 beta, 2, 6, 8, and 10, as well as of tumor necrosis factor-alpha, tra nsforming growth factor-beta and interferon-gamma by a quantitative po lymerase chain reaction. Results: We found high levels of transforming growth factor-beta in post-hepatitis C liver cirrhosis, high to moder ate in alcoholic liver cirrhosis and low in non-cirrhotic specimens. E xpression of interleukin-10, tumor necrosis factor-alpha, and interfer on-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 signific antly 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 hi gh degree of cytokine gene expression, whereas in alcoholic liver cirr hosis it tended to be moderate, and restricted to some cytokines (tran sforming growth factor-beta, interleukin-1, 6 and 8, but not interleuk in-10, tumor necrosis factor-alpha or interferon-gamma). In contrast, most non-cirrhotic specimens showed a restricted and low cytokine gene expression. Conclusions: These data suggest that transforming growth factor-beta may have an important role in liver fibrosis and inflammat ion. Interleukin-1 beta, 6, 8, tumor necrosis factor-alpha and interfe ron-gamma, appear to participate in the pathogenesis of the mild to se vere inflammatory phenomena seen in alcoholic and post-hepatitis C liv er cirrhosis, respectively. Our data suggest that tumor necrosis facto r-alpha does not participate in the hepatocellular damage of alcoholic liver cirrhosis, and indicate that neither interferon-gamma nor inter leukin-10, at least at the levels observed in post-hepatitis C liver c irrhosis, are able to counteract the fibrotic/inflammatory process see n in this condition.