Interleukin-4 Treatment Restores Cellular Immunity After Ethanol Exposure and Burn Injury

Background: Previous 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. Methods: Mice 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. Results: Lymphocytes 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. Conclusions: These 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.