Up-regulation of IL-18 and IL-12 in the ileum of neonatal rats with necrotizing enterocolitis

Melissa D. Halpern, Hana Holubec, Jessica A. Dominguez, Catherine S. Williams, Yolanda G. Meza, Debra L. McWilliam, Claire M. Payne, Robert S. McCuskey, David G. Besselsen, Bohuslav Dvorak

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101 Scopus citations


Necrotizing enterocolitis (NEC) is a common and devastating gastrointestinal disease of premature infants. Because the proinflammatory cytokines IL-18, IL-12, and interferon (IFN)-γ have been implicated in other diseases of the small intestine, we hypothesized that these cytokines would play an important role in NEC pathogenesis. NEC was induced in newborn rats via enteral feeding with rat milk substitute and asphyxia and cold I stress (RMS). Dam-fed, asphyxia- and cold-stressed littermates were used as controls (DF). After 96 h, the distal ileum was removed from all animals and processed to determine expression and localization of IL-18, IL-12, and IFN-γ using real-time reverse transcriptase PCR and immunohistology. IL-18 and IL-12 mRNA from the RMS group were increased (p ≤ 0.05) compared with DF controls, and there was a correlation between increasing IL-18 and IL-12 mRNA levels and progression of I tissue damage (r = 0.629 and 0.588, respectively; p ≤ 0.05). Immunohistology revealed IL-18 in the cytoplasm of villi and crypt enterocytes and IL-12-positive monocytes/macrophages were increased with disease progression (r = 0.503, p ≤ 0.05). No differences in the number of IFN-γ-positive cells were observed between groups. These data demonstrate up-regulation of IL-18 and IL-12 in experimental NEC and a correlation between production of these proinflammatory cytokines and progression of tissue damage.

Original languageEnglish (US)
Pages (from-to)733-739
Number of pages7
JournalPediatric Research
Issue number6
StatePublished - 2002

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health


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