JOURNAL ARTICLE
REVIEW

Anti-inflammatory strategies in alcoholic steatohepatitis

Nobuyuki Enomoto, Yoshiyuki Takei, Shunhei Yamashina, Kenichi Ikejima, Tsuneo Kitamura, Nobuhiro Sato
Journal of Gastroenterology and Hepatology 2007, 22: S59-61
17567468
The hepatotoxic effects of alcohol have been described in detail, but mechanisms underlying the hepatotoxicity have been only partially characterized. Recently, increasing lines of evidence indicate that Kupffer cells play multiple roles in initiation and progression of alcoholic steatohepatitis. After ethanol exposure, Kupffer cells are activated via a mechanism dependent on gut-derived endotoxin, and release active mediators such as proinflammatory cytokines and eicosanoids. These mediators are responsible for the pathophysiology of alcoholic steatohepatitis. This review discusses the current concept of Kupffer cell-mediated steatohepatitis and how it relates to the hypothesis on the mechanism by which alcoholic steatohepetitis is caused, as well as several key issues that have to be addressed in this field: (i) How do Kupffer cells undergo priming and activation during alcoholic steatohepatitis?; (ii) What kind of mediators are involved?; and (iii) How does the concept translate into a strategy for therapeutics of alcoholic steatohepatitis?

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