Ileal cytokine dysregulation in experimental necrotizing enterocolitis is reduced by epidermal growth factor.
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.
Halpern
Melissa D
MD
Department of Pediatrics and Steele Memorial Children's Research Center, University of Arizona, Tucson, Arizona 85750-5073, USA.
Dominguez
Jessica A
JA
Dvorakova
Katerina
K
Holubec
Hana
H
Williams
Catherine S
CS
Meza
Yolanda G
YG
Ruth
Miriam C
MC
Dvorak
Bohuslav
B
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
D016207:Cytokines; D007378:Interleukins; D004815:Epidermal Growth Factor