Chronic alcohol exposure sensitizes mice to galactosamine-induced liver injury through enhanced keratinocyte chemoattractant and defective IL-10 production.

Abstract

BACKGROUND/AIMS:

Alcohol sensitizes the liver to several injuries. The mechanisms leading to this sensitization are poorly defined. In the present study, we developed a mouse model of chronic exposure to alcohol vapours that sensitize mice to galactosamine (GAL) liver injury.

METHODS:

C57BL/6 mice were exposed to ethanol vapours for 10 days. Liver injury was induced by intraperitoneal injection of GAL (1 g/kg) and mice were killed 24 h later.

RESULTS:

GAL challenge after ethanol pre-treatment significantly raised serum alanine aminotransaminase (ALT) levels and enhanced liver inflammation when compared with the controls (GAL alone). Serum keratinocyte chemoattractant (KC) and monocyte chemoattractant protein-1 (MCP-1) levels were significantly increased in the GAL+ethanol group. On the contrary, serum interleukin 10 (IL-10) levels were lower than in controls. Anti-KC, anti-tumour necrosis factor alpha antibodies and intestinal decontamination significantly protected mice from liver injury. In GAL+ethanol-treated mice, IL-10 treatment reduced ALT release, KC and MCP-1 serum and hepatic mRNA levels, and improved liver inflammation.

CONCLUSIONS:

Enhancement of GAL-induced liver injury by ethanol is associated with an imbalance between proinflammatory cytokines and the anti-inflammatory cytokine IL-10 and depends on gut bacterial flora.

• Authors: Filip Sermon, Olivier Le Moine, Thierry Gustot, Eric Quertinmont, Hubert Louis, Nathalie Nagy, Chantal Degraef, Jacques Devière
• Journal: Journal of hepatology (J Hepatol) Vol. 39 Issue 1 Pg. 68-76 (Jul 2003) ISSN: 0168-8278 [Print] Netherlands
• PMID: 12821046 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Central Nervous System Depressants
• Chemokine CCL2
• Tumor Necrosis Factor-alpha
• Interleukin-10
• Ethanol
• Galactosamine

Topics

• Administration, Inhalation
• Animals
• Central Nervous System Depressants (pharmacology)
• Chemokine CCL2 (metabolism)
• Chronic Disease
• Drug Interactions
• Ethanol (pharmacology)
• Female
• Galactosamine (pharmacology)
• Interleukin-10 (metabolism, pharmacology)
• Intestines (microbiology)
• Keratinocytes (cytology)
• Liver Diseases, Alcoholic (immunology, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Tumor Necrosis Factor-alpha (metabolism)