Role of interleukin-18 and its receptor in hepatocellular carcinoma associated with hepatitis C virus infection

✍ Scribed by Masami Asakawa; Hiroshi Kono; Hidetake Amemiya; Masanori Matsuda; Tetsuya Suzuki; Akira Maki; Hideki Fujii

• Publisher: John Wiley and Sons
• Year: 2005
• Tongue: French
• Weight: 339 KB
• Volume: 118
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.21367

✦ Synopsis

Abstract

Interleukin (IL)‐18 is a proinflammatory cytokine that is up‐regulated in patients with hepatitis C virus (HCV) infection, which is the most common underlying disease in hepatocellular carcinoma (HCC). The purpose of our study was to investigate the role of IL‐18 in HCC associated with HCV infection. Sixty‐five patients with HCC and HCV infections who received curative surgical resections were examined in our study. The expression of the IL‐18 receptor was investigated in HCC tissues obtained from these patients and in 2 HCC cell lines. Nuclear factor (NF)‐κB activity and the expression of Bcl‐xL and xIAP mRNA were tested in the cell lines using recombinant human (rh) IL‐18. The IL‐18 receptor was expressed in both the HCC tissues and the cell lines. NF‐κB activation and the expression of Bcl‐xL and xIAP mRNA were increased by rhIL‐18. Moreover, rhIL‐18 suppressed the apoptosis of HCC cells which was induced by etoposide in vitro. The overall survival rate (55.4%) was significantly worse in the IL‐18 receptor‐positive patients than in the IL‐18 receptor‐negative patients (p = 0.015). In a Cox multivariate analysis, the expression of the IL‐18 receptor was found to be a significant predictor of a poor outcome in HCC patients. The expression of the IL‐18 receptor and an antiapoptotic mechanism involving NF‐κB activation in HCC cells may be implicated in a poor patient outcome. © 2005 Wiley‐Liss, Inc.