IL-15 mRNA expression is associated with liver cirrhosis

Backgroun d: Interleukin-15 (IL-15) is expressed in many organs. It generally inhibits apoptosis and increases cellular proliferation and differentiation. Further it was reported that IL-15 is expressed in hepatocytes and supports liver regeneration. However, IL-15's roles in the liver are largely unknown. The aim of our study was to analyze the IL-15 expression in a mouse model of liver fibrosis and IL-15^-/- KO mouse and in human liver tissues. Methods: Total RNA was isolated from mouse and human liver tissue samples and mRNA- expression was analyzed by RT- PCR. Human liver biopsies were analyzed by a pathologist for disease and degree (Child-Pugh classification). Results: Mice treated with CCl4 for 6 weeks developed fibrosis as determined by Sirius red and alpha-SMA staining. RNA expression analysis revealed enhanced levels of IL-15 in liver tissue samples from mice with proven fibrosis compared to normal liver. Furthermore we found in IL-15-/- KO mice developed fibrosis to a less degree than wild type counterparts. Analyzing 218 human liver tissue samples (normal n=39, fibrosis n=39, cirrhosis n=140) we found that IL-15 mRNA expression is significantly enhanced in liver cirrhosis compared to fibrotic and normal liver (p<0,05). No significant differences were observed for IL-15 expression correlated to cirrhotic disease stages (Child-Pugh classification) and between normal and fibrotic liver tissues. Conclusion: IL-15 expression increases during chronic liver injury developing liver cirrhosis and IL-15 is at least in part involved in development of liver cirrhosis. Therefore, we hypothesise that IL-15 might play an important role during the development/ progression of cirrhosis. Thus, IL-15 could serve as a new prognostic marker and potential target for therapeutical strategies.

IL- 15 - fibrosis - cirrhosis