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

• Published in: Journal of hepatology 2003-07, Vol.39 (1), p.68-76
• Main Authors: Sermon, Filip, Le Moine, Olivier, Gustot, Thierry, Quertinmont, Eric, Louis, Hubert, Nagy, Nathalie, Degraef, Chantal, Devière, Jacques
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Alcohol; Animals; Central Nervous System Depressants - pharmacology; Chemokine CCL2 - metabolism; Chronic Disease; Cytokines; Drug Interactions; Ethanol - pharmacology; Female; Galactosamine; Galactosamine - pharmacology; Interleukin-10 - metabolism; Interleukin-10 - pharmacology; Intestines - microbiology; Keratinocytes - cytology; Liver; Liver Diseases, Alcoholic - immunology; Liver Diseases, Alcoholic - metabolism; Liver Diseases, Alcoholic - pathology; Mice; Mice, Inbred C57BL; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/S0168-8278(03)00186-7

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 α 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.