The hypothesis that acute ethanol uptake plus trauma can synergize to increase immunosuppression was tested. We found that, unlike non-alcohol-exposed patients, patients with acute alcohol use prior to trauma have a transient decrease in monocyte tumor necrosis factor α (TNFα) production during the very early postinjury (0-3 days) period. However, TNFα production by these alcoholexposed patients' monocytes (MØ) became hyperelevated late postinjury (>9 days). Consequently, these massively elevated MØ TNFα levels can contribute to posttrauma immunosuppression after acute alcohol use. We also demonstrate that normal monocyte activation with the superantigen, Staphylococcus enterotoxin B (SEB), results in a preferential induction of cellassociated MØ TNFα production, described as characteristic of immunosuppressed trauma patients. Acute in vitro ethanol treatment down-regulated the elevated TNFα production by trauma patients' MØ after either SEB, muramyl-dipeptide (MDP), interferon-γ plus MDP, or lipopolysaccharide (LPS) stimulation. Both SEB- and LPS-induced TNFα mRNA induction was inhibited by acute alcohol treatment in normal MØ, indicating that ethanol can regulate cytokine gene expression. An additional immunosuppressive effect of acute ethanol's stimulation was suggested by its induction of elevated transforming growth factor β production in trauma patients' activated MØ.
- cell-associated tumor necrosis factor α
- prostaglandin E
- transforming growth factor β
ASJC Scopus subject areas
- Immunology and Allergy