title: Ileal cytokine dysregulation in experimental necrotizing enterocolitis is reduced by epidermal growth factor.
abstract: BACKGROUND
  Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants. We have shown in previous studies that proinflammatory interleukin-18 and interleukin-12 are up-regulated in the ileum of rats with experimental NEC and that epidermal growth factor (EGF) reduces the development of disease. Here we investigated whether the protective effects of EGF are a result of changes in ileal interleukin-18, interleukin-12 and/or antiinflammatory interleukin-10.
  
  
  METHODS
  Newborn rats were artificially fed with either growth-factor-free rat milk substitute (RMS) or RMS supplemented with 500 ng/mL EGF (RMS + EGF) and NEC was induced via exposure to asphyxia and cold stress. Cytokine expression and localization were assessed using reverse-transcription real-time polymerase chain reaction and immunohistology/confocal microscopy.
  
  
  RESULTS
  Enteral administration of EGF (RMS + EGF) decreased overproduction of interleukin-18 and increased interleukin-10 production in the ileum. Furthermore, increased interleukin-10 production was associated with up-regulation of the transcription factor Sp1 in RMS + EGF rats.
  
  
  CONCLUSIONS
  These data suggest that EGF may reduce NEC via increased interleukin-10 and decreased interleukin-18 and that EGF-mediated up-regulation of Sp1 may account for the increased interleukin-10.
authors.affiliation: Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona, Tucson, Arizona 85750-5073, USA.
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Halpern
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Dominguez
authors.forename: Katerina
authors.initials: K
authors.lastname: Dvorakova
authors.forename: Hana
authors.initials: H
authors.lastname: Holubec
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Williams
authors.forename: Yolanda G
authors.initials: YG
authors.lastname: Meza
authors.forename: Miriam C
authors.initials: MC
authors.lastname: Ruth
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Dvorak
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016207:Cytokines / Q000187:drug effects*; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000276:immunology* / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007082:Ileum / Q000276:immunology* / Q000378:metabolism*; D007150:Immunohistochemistry; D007378:Interleukins / Q000378:metabolism; D018613:Microscopy, Confocal; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016207:Cytokines; D007378:Interleukins; D004815:Epidermal Growth Factor