Role of interleukin-10 in the pathogenesis of necrotizing enterocolitis

Claudia N. Emami, Nikunj Chokshi, Jin Wang, Catherine Hunter, Yigit Guner, Kerstin Goth, Larry Wang, Anatoly Grishin, Henri R. Ford

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

Background: Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in premature neonates. The pathogenesis of NEC is characterized by an intestinal epithelial injury caused by perinatal insults, leading to the activation of the mucosal innate immune system and exacerbation of the epithelial barrier damage. Cytokines play an important role in mucosal immunity. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that has been shown to play a role in epithelial integrity and modulation of the mucosal immune system. We hypothesized that IL-10 may protect against the development of experimental NEC by blunting the inflammatory response in the intestine. Methods: Wild-type and IL-10 -/- mice underwent a NEC-inducing regimen of formula feeding in combination with hypoxia and hypothermia (FF+HH). Integrity of the gut barrier was assessed through measurement of epithelial apoptosis, tight junction disruption, and inducible nitric oxide synthase. A total of 5 μg of exogenous IL-10 was administered intraperitoneally to IL-10-/-mouse pups before the initiation of FF+HH to test dependence of gene knockout phenotype on IL-10. Results: IL-10 -/- FF+HH showed more severe morphologic and histologic changes compared with controls as evidenced by increased epithelial apoptosis, decreased junctional adhesion molecule-1 localization, and increased intestinal inducible nitric oxide synthase expression. Administration of exogenous IL-10 alleviated the mucosal injury. Conclusions: We conclude that IL-10 plays a protective role in the pathogenesis of NEC by attenuating the degree of intestinal inflammation.

Original languageEnglish (US)
Pages (from-to)428-435
Number of pages8
JournalAmerican journal of surgery
Volume203
Issue number4
DOIs
StatePublished - Apr 2012

Keywords

  • Animal models of NEC
  • Apoptosis
  • IL-10
  • INOS
  • JAM-1
  • Necrotizing enterocolitis (NEC)

ASJC Scopus subject areas

  • Surgery

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    Emami, C. N., Chokshi, N., Wang, J., Hunter, C., Guner, Y., Goth, K., Wang, L., Grishin, A., & Ford, H. R. (2012). Role of interleukin-10 in the pathogenesis of necrotizing enterocolitis. American journal of surgery, 203(4), 428-435. https://doi.org/10.1016/j.amjsurg.2011.08.016