Inhibition of interleukin-22 attenuates bacterial load and organ failure during acute polymicrobial sepsis

Infect Immun. 2007 Apr;75(4):1690-7. doi: 10.1128/IAI.01564-06. Epub 2007 Jan 29.


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.

MeSH terms

  • Animals
  • Blood / microbiology
  • Colony Count, Microbial
  • Disease Models, Animal
  • Hepatocytes / microbiology
  • Interleukins / antagonists & inhibitors*
  • Interleukins / biosynthesis
  • Interleukins / physiology*
  • Kidney / immunology
  • Kidney / microbiology
  • Liver / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Multiple Organ Failure / immunology*
  • Neutrophils / immunology
  • Peritoneal Cavity / microbiology
  • Peritonitis / complications
  • Peritonitis / immunology*
  • Peritonitis / microbiology*
  • Phagocytes / immunology
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • Receptors, Interleukin / biosynthesis
  • Renal Insufficiency / immunology
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT3 Transcription Factor / biosynthesis
  • Sepsis / immunology*
  • Sepsis / microbiology
  • Spleen / immunology


  • Interleukins
  • RNA, Messenger
  • Receptors, Interleukin
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • interleukin-22 receptor
  • interleukin-22