title: Interleukin-22:  implications for liver ischemia-reperfusion injury.
abstract: BACKGROUND
  Ischemia-reperfusion injury (IRI) is common in general surgery and organ transplantation, and in the case of liver, it triggers proinflammatory innate immune cascade and hepatic necrosis, leading to increased incidence of early and late organ rejection. Interleukin (IL)-22, an inducible cytokine of T-cell origin and a member of the IL-10 superfamily, acts on target tissues through IL-22 receptor (IL-22R1).
  
  
  METHODS
  Partial hepatic warm ischemia was induced in C57Bl/6 wild-type (WT) and type 1 interferon receptor-deficient (KO) mice for 90 min followed by 6 to 24 hr of reperfusion. WT mice were treated at 30 min before the ischemia insult with recombinant IL-22 or anti-IL-22 neutralizing antibody; phosphate-buffered saline and IgG served as respective controls.
  
  
  RESULTS
  IL-22 was detected at 24 hr but not 6 hr of liver IRI. The expression of IL-22R1 was increased by 6 hr of reperfusion in WT but not type 1 interferon receptor KO mice that were protected from IRI. Treatment of WT mice with recombinant IL-22 decreased serum aspartate aminotransferase levels, ameliorated cardinal histological features of IR damage (Suzuki's score) and diminished leukocyte sequestration, along with the expression of IL-22R1 and pro-inflammatory cytokines. IL-22 antibody did not appreciably affect IRI but increased IL-22R1 transcription in the liver. Administration of IL-22 protein exerted hepatoprotection by STAT3 activation.
  
  
  CONCLUSIONS
  This is the first report investigating immune modulation by T-cell-derived IL-22 in liver injury caused by warm ischemia and reperfusion. Treatment with IL-22 protein may represent a novel therapeutic strategy to prevent liver IRI in transplant recipients.
authors.affiliation: Division of Liver and Pancreas Transplantation, Department of Surgery, Dumont-UCLA Transplant Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Chestovich
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Uchida
authors.forename: William
authors.initials: W
authors.lastname: Chang
authors.forename: Mark
authors.initials: M
authors.lastname: Ajalat
authors.forename: Charles
authors.initials: C
authors.lastname: Lassman
authors.forename: Robert
authors.initials: R
authors.lastname: Sabat
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Busuttil
authors.forename: Jerzy W
authors.initials: JW
authors.lastname: Kupiec-Weglinski
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage; D004195:Disease Models, Animal; D018836:Inflammation Mediators / Q000378:metabolism; D007378:Interleukins / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008099:Liver / Q000098:blood supply* / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics; D018123:Receptors, Interleukin / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D015427:Reperfusion Injury / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013997:Time Factors; D000097043:Interleukin-22
chemical_list: D057134:Antibodies, Neutralizing; D018836:Inflammation Mediators; D007378:Interleukins; D053633:Receptor, Interferon alpha-beta; D018123:Receptors, Interleukin; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C508034:Ifnar2 protein, mouse; C494087:Stat3 protein, mouse; C415369:interleukin-22 receptor