• Kelly A N Messingham, Scott A Heinrich, Eric M Schilling, and Elizabeth J Kovacs.
• Department of Cell Biology, Neurobiology, and Anatomy, Loyola University Medical Center, Maywood, Illinois, USA.
• Alcohol. Clin. Exp. Res. 2002 Apr 1; 26 (4): 519-26.

BackgroundPrevious studies from this laboratory showed that the suppression of cell-mediated immunity after the combined injury of ethanol exposure and burn is mediated by increased presence of the proinflammatory cytokine interleukin (IL)-6. IL-4 is a T-helper cell type 2 lymphocyte-derived cytokine that serves to down-regulate the inflammatory response. Therefore, the goal of this study was to evaluate the effects of ethanol exposure and burn injury on lymphocyte production of IL-4 and to determine whether administration of IL-4 could improve cellular immunity after ethanol exposure and burn injury through modulation of IL-6 levels.MethodsMice were subjected to a 15% total body-surface area burn (or sham) injury 30 min after being given a single dose of alcohol (or saline) designed to achieve a blood alcohol level of 100 mg/dl. Thirty minutes after burn, mice were treated with IL-4 (or vehicle) and were killed 24 hr later.ResultsLymphocytes from ethanol/burn mice secreted significantly less IL-4 in comparison to all other groups of mice (p < 0.05). Administration of IL-4 resulted in a complete restoration of the delayed-type hypersensitivity (p < 0.01) and splenocyte proliferative responses (p < 0.05) and a significant reduction in circulating and splenic macrophage-derived IL-6 (p < 0.05). Addition of IL-4 (100 or 300 pg/ml) to cultures generated from ethanol/burn and vehicle mice resulted in a complete restoration of splenocyte proliferation and a concomitant attenuation of macrophage IL-6 production.ConclusionsThese studies suggest that the loss of lymphocyte production of IL-4 after ethanol exposure and burn injury may contribute to the exaggerated production of IL-6, a known mediator of immune suppression after injury. Moreover, the administration of IL-4 may be beneficial for patients with injuries that are characterized by a dysregulated inflammatory response.

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