Increased intrahepatic messenger RNA expression of interleukins 2, 6, and 8 in human cirrhosis.

BACKGROUND/AIMS: The role of cytokines in the pathogenesis of chronic liver disease is unclear. The aim of this study was to identify intrahepatic cytokines at the messenger RNA (mRNA) level in end-stage human cirrhosis.

METHODS

Cytokine mRNA expression for interleukin (IL) 1 beta, IL-2, IL-6, IL-8, transforming growth factor beta, interferon gamma, and tumor necrosis factor alpha was examined by semiquantitative polymerase chain reaction in 25 human cirrhotic livers and 13 controls. Cellular localization of IL-8 was performed by immunohistochemistry.

RESULTS

The results show that IL-2 (P < 0.0001), IL-6 (P < 0.0001), IL-8 (P < 0.0001), transforming growth factor beta (P < 0.001), and interferon gamma (P < 0.04) were upregulated in human cirrhosis compared with controls. IL-1 beta and interferon gamma mRNA showed increased expression in cirrhotics with autoimmune chronic active hepatitis compared with those with primary biliary cirrhosis. Immunohistochemistry showed that IL-8 protein was expressed by infiltrating cells in portal tracts and fibrotic septae and within hepatic lobules.

CONCLUSIONS

It is concluded that there is significant activation of cytokines at the mRNA level in end-stage cirrhosis. This suggests continued immune activation even at the late stages of cirrhosis and may indicate the importance of cytokines in the pathogenesis and progression of chronic liver disease.