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Alcohol Clin Exp Res. 2004 Mar;28(3):365-73.

Differential expression of liver interleukin-6 receptor-alpha in female versus male ethanol-consuming rats.

Author information

1
Department of Pharmaceutical Sciences Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190, USA. randy-gallucci@ouhsc.edu

Abstract

BACKGROUND:

It is well known that women are more susceptible to alcoholic liver disease (ALD) than men, and inflammation is thought to play a major role in alcohol-induced liver injury. Increased circulating levels of the proinflammatory cytokine interleukin (IL)-6 are a marker for serious ALD in humans. However, IL-6 also has protective effects, such as induction of liver regeneration and inhibition of hepatocyte apoptosis. Although the roles of IL-6 in ALD have begun to be established, little is known about the expression of its receptor (IL-6Ralpha) during chronic alcohol administration.

METHODS:

Male and female rats were intragastrically fed ethanol or control isocaloric liquid diet for 2 and 4 weeks. Liver samples were collected, and gene expression was assessed by reverse transcription-polymerase chain reaction and Western blot.

RESULTS:

Herein, we show clear gender differences in alcohol-induced liver IL-6Ralpha expression. Analysis of rat liver samples showed that ethanol consumption significantly increased IL-6Ralpha messenger RNA and protein expression in females as compared with similarly treated males after 2 and 4 weeks. Increased STAT3 phosphorylation in the livers of ethanol-consuming females also indicated greater IL-6Ralpha activation in these animals. Conversely, ethanol-consuming males displayed increased IkappaB messenger RNA and protein expression, which may inhibit IL-6R expression, compared with females.

CONCLUSIONS:

Given the association of inflammation with ethanol-induced liver damage, these data may offer insight into a possible mechanism by which females develop more severe ALD than males.

[Indexed for MEDLINE]

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