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


CONCLUSIONS
Tumor necrosis factor alpha antibody may have an attenuating effect on experimental NEC in rats.
Seitz
Guido
G
Department of Pediatric Surgery, University Children's Hospital, 72076 Tübingen, Germany. guido.seitz@med.uni-tuebingen.de
Warmann
Steven W
SW
Guglielmetti
Andres
A
Heitmann
Heike
H
Ruck
Peter
P
Kreis
Martin E
ME
Fuchs
Jörg
J
D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies; D004032:Diet; D004195:Disease Models, Animal; D020345:Enterocolitis, Necrotizing / Q000276:immunology*; D007150:Immunohistochemistry; D007249:Inflammation; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D000906:Antibodies; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase