Role of IL-6 in Gender Differences of Hepatocarcinogenesis

Abstract

Regardless of etiology, hepatocellular carcinoma (HCC) develops much more frequently in males than in females in almost all populations. Although sex hormones and X-chromosome-linked genetic factors are considered to be important, the precise mechanism has not yet been elucidated. Recent clinical and experimental studies have revealed that interleukin-6 (IL-6) and the inflammationmediated signal transduction pathways, including nuclear factor-kappaB (NF-kB), seem to play key roles in the gender difference in hepatocarcinogenesis. In particular, a report by Naugler et al. showing that estrogen-mediated inhibition of IL-6 production by Kupffer cells explains the gender disparity in HCC development, gives considerable attention to the association between IL-6 and hepatocarcinogenesis. Investigating the factors causing a gender difference in hepatocarcinogenesis is very important to clarify the carcinogenic pathway and the therapeutic target for HCC.

Keywords: hepatocellular carcinoma, gender difference, sex hormones, liver inflammation, hepatitis virus, interleukin-6, nuclear factor-kappa B, mitogen-activated protein kinase, signal transducer and activator of transcription 3, microRNA