An alteration of the gut-liver axis drives pulmonary inflammation after intoxication and burn injury in mice Journal Article


Authors: Chen, M. M.; Zahs, A.; Brown, M. M.; Ramirez, L; Turner, J. R.; Choudhry, M. A.; Kovacs, E. J.
Article Title: An alteration of the gut-liver axis drives pulmonary inflammation after intoxication and burn injury in mice
Abstract: Approximately half of all adult burn patients are intoxicated at the time of their injury and have worse clinical outcomes than those without prior alcohol exposure. This study tested the hypothesis that intoxication alters the gut-liver axis, leading to increased pulmonary inflammation mediated by burn-induced IL-6 in the liver. C57BL/6 mice were given 1.2 g/kg ethanol 30 min prior to a 15% total body surface area burn. To restore gut barrier function, the specific myosin light chain kinase inhibitor membrane-permeant inhibitor of kinase (PIK), which we have demonstrated to reduce bacterial translocation from the gut, was administered 30 min after injury. Limiting bacterial translocation with PIK attenuated hepatic damage as measured by a 47% reduction in serum alanine aminotransferase (P 0.05), as well as a 33% reduction in hepatic IL-6 mRNA expression (P 0.05), compared with intoxicated and burn-injured mice without PIK. This mitigation of hepatic damage was associated with a 49% decline in pulmonary neutrophil infiltration (P 0.05) and decreased alveolar wall thickening compared with matched controls. These results were reproduced by prophylactic reduction of the bacterial load in the intestines with oral antibiotics before intoxication and burn injury. Overall, these data suggest that the gut-liver axis is deranged when intoxication precedes burn injury and that limiting bacterial translocation in this setting attenuates hepatic damage and pulmonary inflammation.
Journal Title: American journal of physiology.Gastrointestinal and liver physiology
Volume: 307
Issue: 7
ISSN: 1522-1547; 0193-1857
Publisher: the American Physiological Society  
Journal Place: United States
Date Published: 2014
Start Page: G711
End Page: 8
Language: eng
DOI/URL:
Notes: CI: Copyright (c) 2014; GR: AA-012034/AA/NIAAA NIH HHS/United States; GR: AA-019913/AA/NIAAA NIH HHS/United States; GR: F30 AA-022856/AA/NIAAA NIH HHS/United States; GR: T32 AA-013527/AA/NIAAA NIH HHS/United States; JID: 100901227; 0 (Anti-Bacterial Agents); 0 (Inflammation Mediators); 0 (Interleukin-6); 0 (Protein Kinase Inhibitors); 0 (interleukin-6, mouse); 3K9958V90M (Ethanol); EC 2.7.11.18 (Myosin-Light-Chain Kinase); OID: NLM: PMC4187067 [Available on 10/01/15]; OTO: NOTNLM; PMCR: 2015/10/01 00:00; 2014/08/07 [aheadofprint]; ppublish