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IL-6 deficiency attenuates murine diet-induced non-alcoholic steatohepatitis.

Abstract : BACKGROUND: 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. MATERIALS AND METHODS: Steatohepatitis was induced by feeding wild-type or IL-6(-/-) mice for 5 weeks with a methionine and choline-deficient (MCD) diet. RESULTS: Whereas MCD diet-induced weight loss and decreases in serum glucose, cholesterol and triglyceride levels were similar in both genotypes, serum alanine aminotransferase was less elevated in IL-6(-/-) mice than in wild-type animals. Despite having a comparable liver steatosis score, IL-6-deficient mice exhibited less lobular inflammation than their wild-type littermates. Liver gene expression of TGF-beta and MCP-1 was also strongly attenuated in mutant mice; a more modest reduction was observed for PPAR-gamma and F4/80 transcripts as well as proteins. Chromatographic analysis of liver lipids demonstrated that MCD diet induced in normal and mutant mice a similar decrease in the ratio of phosphatidylcholine to phosphatidylethanolamine. However, the diet-induced increase in the levels of sphingomyelin and ceramide was less important in IL-6(-/-) mice. CONCLUSION: Altogether, these results indicate that IL-6 deficiency does not block the development of NASH; yet, IL-6 plays a critical role in the accompanying liver inflammation.
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Submitted on : Monday, April 26, 2010 - 11:34:26 AM
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Emmanuel Mas, Marie Danjoux, Virginie Garcia, Stéphane Carpentier, Bruno Ségui, et al.. IL-6 deficiency attenuates murine diet-induced non-alcoholic steatohepatitis.. PLoS ONE, Public Library of Science, 2009, 4 (11), pp.e7929. ⟨10.1371/journal.pone.0007929⟩. ⟨inserm-00474274⟩



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