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(Journal of Leukocyte Biology. 2002;72:1142-1147.)
© 2002 by Society for Leukocyte Biology

Ethanol-induced inhibition of cytokine release and protein degranulation in human neutrophils

Julien Taïeb*,{dagger}, Charlotte Delarche*, Fréderic Ethuin*, Saphia Selloum*, Thierry Poynard{dagger}, Marie-Anne Gougerot-Pocidalo* and Sylvie Chollet-Martin*

* Service d’Immunologie et d’Hématologie et INSERM U479, CHU Xavier Bichat, Paris, France; and
{dagger} Service d’Hépato-gastroentérologie, CHU Pitié Salpêtrière, Paris, France

Correspondence: Dr. Sylvie Chollet-Martin, Service d’Hématologie et d’Immunologie Biologiques, CHU Xavier Bichat, 46, rue Henri-Huchard, 75877 Paris cedex 18-France. E-mail: sylvie.martin{at}bch.ap-hop-paris.fr

Ethanol impairs immune responses in humans and animal models, in vivo and in vitro. In particular, ethanol inhibits some key functions of human polymorphonuclear neutrophils (PMN). We investigated the impact of ethanol on cytokine production by highly purified PMN. In a time- and concentration-dependent manner, ethanol inhibited the production of interleukin (IL)-8 protein and mRNA and also hindered tumor necrosis factor {alpha} (TNF-{alpha}) release by modulating the expression of the TNF-{alpha}-converting enzyme involved in TNF-{alpha} shedding. This disruption of PMN cytokine release by ethanol may contribute to the increased risk of infection in alcoholic patients. Degranulation of hepatocyte growth factor (HGF) was also impaired by a clinically relevant ethanol concentration (0.8%), an action that may delay the repair of alcoholic liver damage. These findings suggest that ethanol may modulate three major cytokines involved in alcoholic liver diseases, IL-8, TNF-{alpha}, and HGF, via three different mechanisms.

Key Words: IL-8 • TNF-{alpha} • HGF • TACE




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