Acute alcohol intoxication reduces mortality, inflammatory responses and hepatic injury after haemorrhage and resuscitation in vivo

• Published in: British journal of pharmacology Vol. 165; no. 4b; pp. 1188 - 1199
• Main Authors: Relja, B, Höhn, C, Bormann, F, Seyboth, K, Henrich, D, Marzi, I, Lehnert, M
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.02.2012
• Subjects: Alanine Transaminase - blood; Alcoholic Intoxication; Animals; Cytokines - blood; Cytokines - genetics; Cytokines - immunology; ethanol; Ethanol - administration & dosage; Female; Gene Expression - drug effects; I-kappa B Proteins - metabolism; in vivo; inflammation; Inflammation - pathology; Inflammation - physiopathology; Inflammation - prevention & control; Intercellular Adhesion Molecule-1 - metabolism; Lipid Metabolism; liver; Liver Diseases - pathology; Liver Diseases - physiopathology; Liver Diseases - prevention & control; Matrix Metalloproteinase 9 - metabolism; Mortality; Neutrophils - immunology; NF-KappaB Inhibitor alpha; Rats; Rats, Inbred Lew; Research Papers; Resuscitation; Shock, Hemorrhagic; survival
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.2011.01595.x

BACKGROUND AND PURPOSE Haemorrhagic shock and resuscitation (H/R) induces hepatic injury, strong inflammatory changes and death. Alcohol intoxication is assumed to worsen pathophysiological derangements after H/R. Here, we studied the effects of acute alcohol intoxication on survival, liver injury and inflammation after H/R, in rats. EXPERIMENTAL APPROACH Rats were given a single oral dose of ethanol (5 g·kg−1, 30%) or saline (control), 12 h before they were haemorrhaged for 60 min and resuscitated (H/R). Sham groups received the same procedures without H/R. Measurements were made 2, 24 and 72 h after resuscitation. Survival was assessed 72 h after H/R. KEY RESULTS Ethanol increased survival after H/R three‐fold and also induced fatty changes in the liver. H/R‐induced liver injury was amplified by ethanol at 2 h but inhibited 24 h after H/R. Elevated serum IL‐6 levels as well as hepatic IL‐6 and TNF‐α gene expression 2 h after H/R were reduced by ethanol. Ethanol enhanced serum IL‐1β at 2 h, but did not affect increased hepatic IL‐1β expression at 72 h after H/R. Local inflammatory markers, hepatic infiltration with polymorphonuclear leukocytes and intercellular adhesion molecule 1 expression decreased after ethanol compared with saline, following H/R. Ethanol reduced H/R‐induced IκBα activation 2 h after H/R, and NF‐κB‐dependent gene expression of MMP9. CONCLUSIONS AND IMPLICATIONS Ethanol reduced H/R‐induced mortality at 72 h, accompanied by a suppression of proinflammatory changes after H/R in ethanol‐treated animals. Binge‐like ethanol exposure modulated the inflammatory response after H/R, an effect that was associated with NF‐κB activity.