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Am J Physiol Gastrointest Liver Physiol 287: G497-G502, 2004; doi:10.1152/ajpgi.00171.2004
0193-1857/04 $5.00
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THEMES

Recent Advances in Alcoholic Liver Disease IV. Dysregulated cytokine metabolism in alcoholic liver disease

Craig J. McClain, Zhenyuan Song, Shirish S. Barve, Daniell B. Hill, and Ion Deaciuc

Department of Internal Medicine, University of Louisville Medical Center, Louisville, Kentucky 40292

Submitted 27 April 2004 ; accepted in final form 11 May 2004

Alcoholic liver disease (ALD) remains a leading cause of death from liver disease in the United States for which there is no FDA-approved therapy. Abnormal cytokine metabolism is a major feature of ALD. Elevated serum concentration levels of TNF-{alpha} and TNF-{alpha}-inducible cytokines/chemokines, such as IL-6, -8, and -18, have been reported in patients with alcoholic hepatitis and/or cirrhosis, and levels correlated with markers of the acute phase response, liver function, and clinical outcome. Studies in animal models support an etiologic role for cytokines in the liver injury of ALD. Cytokines, such as transforming growth factor-{beta}, play a critical role in the fibrosis of ALD. Multiple new strategies are under investigation to modulate cytokine metabolism as a form of therapy for ALD.

tumor necrosis factor; cytokines; oxidative stress; necrosis; apoptosis


Address for reprint requests and other correspondence: C. J. McClain, Dept. of Internal Medicine, Univ. of Louisville Medical Center, 550 S. Jackson St., ACB 3rd Floor, Louisville, KY 40292 (E-mail: craig.mcclain{at}louisville.edu)




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