INTERLEUKIN-22 MODULATES GUT EPITHELIAL AND IMMUNE BARRIER FUNCTIONS FOLLOWING ACUTE ALCOHOL EXPOSURE AND BURN INJURY

Interleukin-22 (IL-22) maintains gut epithelial integrity and expression of antimicrobial peptides Reg3 beta and Reg3 gamma. Our laboratory has shown that acute alcoho/ethanol (EtOH) exposure before burn injury results in increased gut permeability, intestinal T-cell suppression, and enhanced bacterial translocation. Herein, we determined the effect of combined EtOH intoxication and burn injury on intestinal levels of IL-22 as well as Reg3 beta and Reg3 gamma expression. We further examined whether in vivo restitution of IL-22 restores gut permeability, Reg3 beta and Reg3 gamma levels, and bacterial load (e.g., gut bacterial growth) within the intestine after EtOH and burn injury. Male mice, similar to 25g, were gavaged with EtOH (2.9 mg/kg) before receiving a similar to 12.5% total-body-surface-area, full-thickness burn. Mice were immediately treated with saline control or IL-22 (1 mg/kg) by i.p. injection. One day after injury, there was a significant decrease in intestinal IL-22, Reg3 beta, and Reg3 gamma expression along with an increase in intestinal permeability and gut bacterial load after EtOH combined with burn injury, as compared with sham injury. Treatment with IL-22 normalized Reg3 beta and Reg3 gamma expression and attenuated the increase in intestinal permeability after EtOH and burn injury. Qualitatively, IL-22 treatment reduced the bacterial load in nearly half of mice receiving EtOH combined with burn injury. Our data indicate that IL-22 maintains gut epithelial and immune barrier integrity after EtOH and burn injury; thus, the IL-22/antimicrobial peptide pathway may provide a therapeutic target for the treatment of patients who sustain burn injury under the influence of EtOH.