Inhibition of interleukin-22 attenuates bacterial load and organ failure during acute polymicrobial sepsis.
Interleukin-22 (IL-22) is a recently discovered proinflammatory cytokine, structurally related to IL-10. Since IL-22 is induced by lipopolysaccharide in vivo, we studied the role of IL-22 in a model of polymicrobial peritonitis. Quantitative real-time reverse transcription-PCR analysis showed marked induction of IL-22 and IL-22 receptor in spleen and kidney during the course of sepsis. The biological activity of IL-22 is modulated by IL-22-binding protein (IL-22BP), which is considered a natural antagonist of IL-22. To further analyze the role of IL-22 during septic peritonitis, mice were treated with recombinant IL-22BP generated as Fcgamma2a fusion protein. IL-22BP-Fc completely blocked IL-22-induced STAT3 activation in hepatocytes in vitro. Treatment of mice with IL-22BP-Fc 4 h before sepsis induction led to enhanced accumulation of neutrophils and mononuclear phagocytes and a reduced bacterial load at the site of infection. In addition, IL-22 blockade led to an enhanced bacterial clearance in liver and kidney and reduced kidney injury. These results imply an important proinflammatory role of IL-22 during septic peritonitis, contributing to bacterial spread and organ failure. IL-22 therefore appears to play an important role in the regulation of inflammatory processes in vivo.
Weber
Georg F
GF
Department of Surgery, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany.
Schlautkötter
Sylvia
S
Kaiser-Moore
Simone
S
Altmayr
Felicitas
F
Holzmann
Bernhard
B
Weighardt
Heike
H
D000818:Animals; D001769:Blood / Q000382:microbiology; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000382:microbiology; D007378:Interleukins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology*; D007668:Kidney / Q000276:immunology / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D010529:Peritoneal Cavity / Q000382:microbiology; D010538:Peritonitis / Q000150:complications / Q000276:immunology* / Q000382:microbiology*; D010586:Phagocytes / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D018123:Receptors, Interleukin / Q000096:biosynthesis; D051437:Renal Insufficiency / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000096:biosynthesis; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology; D013154:Spleen / Q000276:immunology; D000097043:Interleukin-22
D007378:Interleukins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; D000097043:Interleukin-22; C494087:Stat3 protein, mouse; C415369:interleukin-22 receptor