title: Interleukin-22 modulates gut epithelial and immune barrier functions following acute alcohol exposure and burn injury.
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.
authors.affiliation: Alcohol Research Program, Loyola University Health Sciences Division, Maywood, IL, USA.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Rendon
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Li
authors.forename: Suhail
authors.initials: S
authors.lastname: Akhtar
authors.forename: Mashkoor A
authors.initials: MA
authors.lastname: Choudhry
mesh_terms: D000249:Adenosine Monophosphate / Q000096:biosynthesis; D000435:Alcoholic Intoxication / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D058491:Bacterial Load; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002056:Burns / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005786:Gene Expression Regulation / Q000276:immunology; D018928:Immunity, Mucosal; D007378:Interleukins / Q000378:metabolism / Q000627:therapeutic use*; D007408:Intestinal Absorption / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology / Q000382:microbiology; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000073718:Pancreatitis-Associated Proteins; D010539:Permeability; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D000097043:Interleukin-22
chemical_list: D000249:Adenosine Monophosphate; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D007378:Interleukins; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; D011506:Proteins; D011994:Recombinant Proteins; D000097043:Interleukin-22; C490255:Reg3g protein, mouse