Interleukin-22 modulates gut epithelial and immune barrier functions following acute alcohol exposure and burn injury

Shock. 2013 Jan;39(1):11-8. doi: 10.1097/SHK.0b013e3182749f96.

Abstract

Interleukin-22 (IL-22) maintains gut epithelial integrity and expression of antimicrobial peptides Reg3β and Reg3γ. Our laboratory has shown that acute alcohol/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 Reg3β and Reg3γ expression. We further examined whether in vivo restitution of IL-22 restores gut permeability, Reg3β and Reg3γ levels, and bacterial load (e.g., gut bacterial growth) within the intestine after EtOH and burn injury. Male mice, ∼25g, were gavaged with EtOH (2.9 mg/kg) before receiving a ∼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, Reg3β, and Reg3γ 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 Reg3β and Reg3γ 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Monophosphate / biosynthesis
  • Alcoholic Intoxication / complications
  • Alcoholic Intoxication / immunology*
  • Alcoholic Intoxication / microbiology
  • Animals
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics
  • Bacterial Load
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics
  • Burns / complications
  • Burns / drug therapy*
  • Burns / immunology
  • Burns / microbiology
  • Disease Models, Animal
  • Drug Evaluation, Preclinical / methods
  • Gene Expression Regulation / immunology
  • Immunity, Mucosal
  • Interleukins / metabolism
  • Interleukins / therapeutic use*
  • Intestinal Absorption / immunology
  • Intestinal Mucosa / immunology
  • Intestine, Small / immunology
  • Intestine, Small / microbiology
  • Lectins, C-Type / biosynthesis
  • Lectins, C-Type / genetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Pancreatitis-Associated Proteins
  • Permeability
  • Proteins / genetics
  • Proteins / metabolism
  • Recombinant Proteins / therapeutic use

Substances

  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Interleukins
  • Lectins, C-Type
  • Pancreatitis-Associated Proteins
  • Proteins
  • Recombinant Proteins
  • Reg3g protein, mouse
  • Adenosine Monophosphate
  • interleukin-22