Protective effect of tumor necrosis factor alpha antibody on experimental necrotizing enterocolitis in the rat

J Pediatr Surg. 2005 Sep;40(9):1440-5. doi: 10.1016/j.jpedsurg.2005.05.043.

Abstract

Background: Necrotizing enterocolitis (NEC) is a common and devastating disorder of premature infants. Elevated proinflammatory cytokines, especially tumor necrosis factor alpha (TNF-alpha), have been implicated in the pathogenesis of NEC. The aim of this study was to evaluate the effects of TNF-alpha on the inflammatory response in NEC by immunoneutralizing TNF-alpha with a selective antibody.

Methods: Neonatal Sprague-Dawley rats were divided in 3 groups: group 1 (n = 20), a NEC-like enterocolitis was induced by formula feeding, asphyxia, and cold exposure; group 2 (n = 9), animals were treated like in group 1 and additionally received TNF-alpha antibody intraperitoneally; and group 3 (n = 17), animals were dam-fed (controls). Animals were killed in case of imminent death or after 96 hours. Specimens from small bowel were processed for blinded histologic (H&E) and immunhistologic (myeloperoxidase [MPO]) analysis.

Results: In group 1, animals developed severe NEC (mean NEC score, 3.28 +/- 0.32; mean MPO, 65.85 +/- 9.46). In group 2, animals developed mild NEC (mean NEC score, 1.72 +/- 0.41; mean MPO, 34.33 +/- 9.69; P < .05). In group 3, no NEC was induced (mean NEC score, 0.0 +/- 0; mean MPO, 6 +/- 1.32; P < .05).

Conclusion: Tumor necrosis factor alpha antibody may have an attenuating effect on experimental NEC in rats.

MeSH terms

  • Animals
  • Animals, Newborn
  • Antibodies
  • Diet
  • Disease Models, Animal
  • Enterocolitis, Necrotizing / immunology*
  • Immunohistochemistry
  • Inflammation
  • Peroxidase / analysis
  • Rats
  • Rats, Sprague-Dawley
  • Severity of Illness Index
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Antibodies
  • Tumor Necrosis Factor-alpha
  • Peroxidase