Date Published: November 20, 2009
Publisher: Public Library of Science
Author(s): Emmanuel Mas, Marie Danjoux, Virginie Garcia, Stéphane Carpentier, Bruno Ségui, Thierry Levade, Irene Oi-Lin Ng. http://doi.org/10.1371/journal.pone.0007929
Abstract: The role of inflammation in the pathogenesis of non-alcoholic steatohepatitis (NASH), a common cause of liver disease, is still poorly understood. This study aimed at assessing the involvement of a major inflammatory cytokine, IL-6, in NASH.
Partial Text: The term non-alcoholic steatohepatitis (NASH) was first used in 1980 by Ludwig et al.  to describe a histological pattern that mimicked alcoholic hepatitis but occurred in patients without history of alcohol abuse. The features of NASH on liver biopsy include steatosis, inflammation, liver cell injury and varying degrees of fibrosis. NASH belongs to the spectrum of non-alcoholic fatty liver disease (NAFLD) and is becoming a major public health problem because it is associated with obesity, insulin resistance and the metabolic syndrome. Therefore, NASH is believed to affect approximately 3% of adults in Western countries and represents, together with alcohol and hepatitis C virus infection, one of the main etiologies of cirrhosis .
The role of inflammatory cytokines in the development of NASH has not yet been fully elucidated. Despite recent studies on different rodent models, the contribution of TNFα to the pathogenesis of NASH remains unclear. Indeed, studies on mice deficient for TNFα or its receptors using different conditions to induce liver steatosis have not led to unequivocal conclusions. The emerging idea is that TNFα is not a primary mediator of NASH but influences its development , , . As to IL-6, its contribution to NASH has remained almost totally elusive. Using a well-established nutritional model of NASH induction –, the present study demonstrates that IL-6 certainly participates to the NASH-associated inflammation but is dispensable for the appearance of the disease. Whereas liver inflammation was markedly reduced in mice deficient for IL-6, as revealed both histologically and by analysing gene expression, liver injury and changes in lipid composition and peroxidation still occurred in mutant mice.