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: Paul J Chestovich, Yoichiro Uchida, William Chang, Mark Ajalat, Charles Lassman, Robert Sabat, Ronald W Busuttil, Jerzy W Kupiec-Weglinski
• Journal: Transplantation (Transplantation) Vol. 93 Issue 5 Pg. 485-92 (Mar 15 2012) ISSN: 1534-6080 [Electronic] United States
• PMID: 22262131 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Neutralizing
• Ifnar2 protein, mouse
• Inflammation Mediators
• Interleukins
• Receptors, Interleukin
• Recombinant Proteins
• STAT3 Transcription Factor
• Stat3 protein, mouse
• interleukin-22 receptor
• Receptor, Interferon alpha-beta

Topics

• Animals
• Antibodies, Neutralizing (administration & dosage)
• Disease Models, Animal
• Inflammation Mediators (metabolism)
• Interleukins (administration & dosage, antagonists & inhibitors, metabolism)
• Liver (blood supply, immunology, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Receptor, Interferon alpha-beta (deficiency, genetics)
• Receptors, Interleukin (metabolism)
• Recombinant Proteins (metabolism)
• Reperfusion Injury (immunology, pathology, prevention & control)
• STAT3 Transcription Factor (metabolism)
• Time Factors
• Interleukin-22