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Background: Burned patients with detectable blood alcohol levels (BAL) show an elevated mortality rate. Interleukin (IL)-6 and reactive oxygen species (ROS) production is stimulated independently by alcohol and burn injury. The aim of the study was to determine whether increasing levels of alcohol differentially enhance the hepatic production of IL-6 and ROS after burn in a murine model of dorsal scald injury. Groups of mice received either saline or alcohol intraperitoneally to reach a BAL of 100 mg/dl or 300 mg/dl at the time of burn (15% total body surface scald) or sham injury., Results: Burn injury alone resulted in a low mortality rate at 24 hr after injury as did the burn group with a BAL of 100 mg/dl (15%), whereas 57% of the mice burned with a BAL of 300 mg/dl did not survive (p = 0.02). Twenty-four hours after burn or sham injury, IL-6 levels were measured by enzyme-linked immunosorbent assay in serum and liver. In the saline-treated group, IL-6 circulating and hepatic levels rose after burn injury (p < 0.03). Circulating IL-6 levels in sham mice increased 1.5-fold in the group with a BAL of 100 mg/dl and 3-fold in those with a BAL of 300 mg/ml (p = 0.005 versus burn-injured, saline-treated). IL-6 hepatic production after burn injury was higher in the mice with a BAL of 300 mg/dl than in those with a BAL of 100 mg/dl and the saline-treated group (p = 0.001). Among the burned mice, alcohol exposure increased hepatic ROS production, measured by lipid peroxidation and protein oxidation, in a dose-dependent manner., Conclusions: Alcohol enhances in a dose-dependent manner the hepatic production of IL-6 induced by burn injury through the modulation of oxidative stress. The increased mortality rate of mice exposed to alcohol and burn injury may be due to the adverse effect on immune function induced by IL-6 elevation.

Background: Previous studies from this laboratory reported that suppression of cell-mediated immune function was coincident with elevated interleukin (IL)-6 production after acute ethanol exposure before burn trauma, compared with either insult alone. The goal of this study was to investigate whether treatment with an anti-IL-6 antibody could restore immunocompetence in mice subjected to burn trauma with previous exposure to alcohol, as assessed by delayed-type hypersensitivity (DTH) and mitogen-induced splenocyte proliferative responses., Methods: Mice given an ethanol treatment designed to reach a blood alcohol level of 100 mg/dl before a 15% total body surface area burn injury were treated with an anti-IL-6 antibody at 30 min and 24 hr postinjury., Results: Burn/ethanol mice exhibited a 91% suppression of the DTH response ( < 0.01) and a 76% suppression of mitogen-induced splenocyte proliferation (p < 0.01) at 48 hr postinjury, along with increased levels of circulating and splenic macrophage-derived IL-6, compared with all other treatment groups. After anti-IL-6 antibody administration to burn/ethanol mice, there was a 25% (p < 0.05) and 63% (p < 0.01) recovery of the DTH and splenocyte proliferative responses, respectively. Addition of exogenous IL-6 to splenocyte cultures isolated from anti-IL-6 antibody-treated burn/ethanol mice resulted in a 70% inhibition of mitogen-induced proliferative responses (p < 0.03)., Conclusions: These data confirm previous findings that burn in combination with acute ethanol exposure suppresses cell-mediated immune function compared with either insult alone. Furthermore, the ability of the anti-IL-6 antibody treatment to improve cellular immune responses in the burn/ethanol group suggests that blocking this cytokine may be beneficial for the ethanol-exposed, thermally injured individual.

To understand the mechanism of suppressed immunity following alcohol consumption and thermal injury, we analyzed T cell functions in a mouse model of acute alcohol exposure and burn injury. Mice with blood alcohol levels at approximately 100 mg/dl were given a 15% scald or sham injury. Mice were sacrificed 48 h after injury. Our data demonstrated a 20-25% decrease in Con A-mediated splenic T cell proliferation (p<0.01) and 45-50% decrease in interleukin-2 (IL-2) production (p<0.01) following burn injury compared to the T cells from sham animals. A further decrease in the proliferation (25-30%) and IL-2 production (40-45%) was detected in T cells derived from burned animals receiving alcohol as compared to burn alone. No significant change in the proliferation and IL-2 production was observed in splenic T cells derived from sham-injured mice regardless of alcohol exposure. Additionally, there was no demonstrable difference in splenocyte apoptosis in any treatment group. These results suggest that alcohol consumption prior to burn injury causes a greater decrease in T cell proliferation and IL-2 production compared to either burn or alcohol injury alone that may further attenuate the cell-mediated immunity and thus enhance susceptibility to infection.