Chronic alcohol exposure sensitizes mice to galactosamine-induced liver injury through enhanced keratinocyte chemoattractant and defective IL-10 production.
OBJECTIVE
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.
Sermon
Filip
F
Laboratory of Experimental Gastroenterology, Hopital Erasme, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium.
Le Moine
Olivier
O
Gustot
Thierry
T
Quertinmont
Eric
E
Louis
Hubert
H
Nagy
Nathalie
N
Degraef
Chantal
C
Devière
Jacques
J
D000280:Administration, Inhalation; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology; D018932:Chemokine CCL2 / Q000378:metabolism*; D002908:Chronic Disease; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D005688:Galactosamine / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism* / Q000494:pharmacology; D007422:Intestines / Q000382:microbiology; D015603:Keratinocytes / Q000166:cytology; D008108:Liver Diseases, Alcoholic / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002492:Central Nervous System Depressants; D018932:Chemokine CCL2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000431:Ethanol; D005688:Galactosamine