Inflammation, HCC and sex: IL-6 in the centre of the triangle
Liver Unit and Division of Hepatology and Gene Therapy, University Clinic and Center for Applied Medical Research, CIBERehd University of Navarra, Pamplona, Spain
Magazine: Journal of Hepatology
Date: Feb 1, 2008Hepatology
Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production.
Hepatocellular carcinoma (HCC), the most common liver cancer, occurs mainly in men. Similar gender disparity is seen in mice given a chemical carcinogen, diethylnitrosamine (DEN). DEN administration caused greater increases in serum interleukin-6 (IL-6) concentration in males than it did in females. Furthermore, ablation of IL-6 abolished the gender differences in hepatocarcinogenesis in mice. DEN exposure promoted production of IL-6 in Kupffer cells (KCs) in a manner dependent on the Toll-like receptor adaptor protein MyD88, ablation of which also protected male mice from DEN-induced hepatocarcinogenesis.
Estrogen inhibited secretion of IL-6 from KCs exposed to necrotic hepatocytes and reduced circulating concentrations of IL-6 in DEN-treated male mice. We propose that estrogen-mediated inhibition of IL-6 production by KCs reduces liver cancer risk in females, and these findings may be used to prevent HCC in males.
CITATION J Hepatol. 2008 Feb;48(2):380-1
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