title: Role of interleukin-10 in the pathogenesis of necrotizing enterocolitis.
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.
authors.affiliation: Department of Surgery, University of Southern California Keck School of Medicine, Children's Hospital Los Angeles, Los Angeles, CA 90027, USA.
authors.forename: Claudia N
authors.initials: CN
authors.lastname: Emami
authors.forename: Nikunj
authors.initials: N
authors.lastname: Chokshi
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.forename: Catherine
authors.initials: C
authors.lastname: Hunter
authors.forename: Yigit
authors.initials: Y
authors.lastname: Guner
authors.forename: Kerstin
authors.initials: K
authors.lastname: Goth
authors.forename: Larry
authors.initials: L
authors.lastname: Wang
authors.forename: Anatoly
authors.initials: A
authors.lastname: Grishin
authors.forename: Henri R
authors.initials: HR
authors.lastname: Ford
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D005260:Female; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II