PMID- 12821046 OWN - NLM STAT- MEDLINE DCOM- 20040311 LR - 20190817 IS - 0168-8278 (Print) IS - 0168-8278 (Linking) VI - 39 IP - 1 DP - 2003 Jul TI - Chronic alcohol exposure sensitizes mice to galactosamine-induced liver injury through enhanced keratinocyte chemoattractant and defective IL-10 production. PG - 68-76 AB - 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. FAU - Sermon, Filip AU - Sermon F AD - Laboratory of Experimental Gastroenterology, Hopital Erasme, Universite Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium. FAU - Le Moine, Olivier AU - Le Moine O FAU - Gustot, Thierry AU - Gustot T FAU - Quertinmont, Eric AU - Quertinmont E FAU - Louis, Hubert AU - Louis H FAU - Nagy, Nathalie AU - Nagy N FAU - Degraef, Chantal AU - Degraef C FAU - Deviere, Jacques AU - Deviere J LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Netherlands TA - J Hepatol JT - Journal of hepatology JID - 8503886 RN - 0 (Central Nervous System Depressants) RN - 0 (Chemokine CCL2) RN - 0 (Tumor Necrosis Factor-alpha) RN - 130068-27-8 (Interleukin-10) RN - 3K9958V90M (Ethanol) RN - 7535-00-4 (Galactosamine) SB - IM MH - Administration, Inhalation MH - Animals MH - Central Nervous System Depressants/pharmacology MH - Chemokine CCL2/*metabolism MH - Chronic Disease MH - Drug Interactions MH - Ethanol/pharmacology MH - Female MH - Galactosamine/*pharmacology MH - Interleukin-10/*metabolism/pharmacology MH - Intestines/microbiology MH - Keratinocytes/cytology MH - Liver Diseases, Alcoholic/*immunology/*metabolism/pathology MH - Mice MH - Mice, Inbred C57BL MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 2003/06/25 05:00 MHDA- 2004/03/12 05:00 CRDT- 2003/06/25 05:00 PHST- 2003/06/25 05:00 [pubmed] PHST- 2004/03/12 05:00 [medline] PHST- 2003/06/25 05:00 [entrez] AID - S0168827803001867 [pii] AID - 10.1016/s0168-8278(03)00186-7 [doi] PST - ppublish SO - J Hepatol. 2003 Jul;39(1):68-76. doi: 10.1016/s0168-8278(03)00186-7.