Ethanol feeding inhibits proinflammatory cytokine expression from murine alveolar macrophages ex vivo.
The prolonged and excessive consumption of alcohol has been shown to predispose the host to a variety of infectious complications, which may be due, in part, to the inability to produce important activating and chemotactic cytokines. In this study, we assessed the effect of alcohol ingestion on the expression of tumor necrosis factor-alpha (TNF-alpha), and the chemokines macrophage inflammatory protein-2 (MIP-2) and macrophage inflammatory protein-1 alpha (MIP-1 alpha) from murine alveolar macrophages (AMs) cultured ex vivo. Two-week ethanol feeding resulted in substantial impairment in the lipopolysaccharide (LPS)-induced expression of TNF-alpha, MIP-2, and MIP-1 alpha mRNA, and protein from LPS-stimulated AMs, compared with cytokine production from AMs obtained from CD-1 mice receiving an isocaloric control diet. These findings indicate that ethanol feeding results in diminished production of chemotactic and/or activating cytokines from AMs ex vivo that may contribute to the impairment in lung inflammatory responses and antimicrobial host defense that is observed in the setting of alcohol ingestion/intoxication clinically and experimentally.
Standiford
T J
TJ
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0360, USA.
Danforth
J M
JM
D000437:Alcoholism / Q000276:immunology*; D000818:Animals; D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000235:genetics / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D015846:Monokines / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D054407:Chemokine CCL4; D054426:Chemokine CXCL2; D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D019402:Macrophage Inflammatory Proteins; D015846:Monokines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha