Interleukin-22 Prevents Microbial Dysbiosis and Promotes Intestinal Barrier Regeneration Following Acute Injury

Shock. 2017 Dec;48(6):657-665. doi: 10.1097/SHK.0000000000000900.

Abstract

Intestine barrier disruption and bacterial translocation can contribute to sepsis and multiple organ failure, leading causes of mortality in burn-injured patients. In addition, findings suggest that ethanol (alcohol) intoxication at the time of injury worsens symptoms associated with burn injury. We have previously shown that interleukin-22 (IL-22) protects from intestinal leakiness and prevents overgrowth of gram-negative bacteria following ethanol and burn injury, but how IL-22 mediates these effects has not been established. Here, utilizing a mouse model of ethanol and burn injury, we show that the combined insult results in a significant loss of proliferating cells within small intestine crypts and increases Enterobacteriaceae copies, despite elevated levels of the antimicrobial peptide lipocalin-2. IL-22 administration restored numbers of proliferating cells within crypts, significantly increased Reg3β, Reg3γ, lipocalin-2 AMP transcript levels in intestine epithelial cells, and resulted in complete reduction of Enterobacteriaceae in the small intestine. Knockout of signal transducer and activator of transcription factor-3 (STAT3) in intestine epithelial cells resulted in complete loss of IL-22 protection, demonstrating that STAT3 is required for intestine barrier protection following ethanol combined with injury. Together, these findings suggest that IL-22/STAT3 signaling is critical to gut barrier integrity and targeting this pathway may be of beneficial clinical relevance following burn injury.

MeSH terms

  • Acute Disease
  • Alcoholic Intoxication* / complications
  • Alcoholic Intoxication* / immunology
  • Alcoholic Intoxication* / microbiology
  • Alcoholic Intoxication* / pathology
  • Animals
  • Bacterial Translocation / drug effects*
  • Burns* / complications
  • Burns* / immunology
  • Burns* / microbiology
  • Burns* / pathology
  • Dysbiosis* / etiology
  • Dysbiosis* / immunology
  • Dysbiosis* / pathology
  • Enterobacteriaceae / immunology*
  • Interleukins / immunology*
  • Intestinal Mucosa* / immunology
  • Intestinal Mucosa* / microbiology
  • Intestinal Mucosa* / pathology
  • Mice
  • Mice, Knockout

Substances

  • Interleukins
  • interleukin-22