Abstract
Background: Necrotizing Enterocolitis (NEC) is the most common gastrointestinal disease predominately affecting premature infants. Pro-inflammatory cytokines, such as TNF-a, have been implicated in intestinal inflammatory diseases. Previously, we have shown that Kupffer cells in the liver are the major producer of TNF-a found in the intestinal luminal contents during experimental NEC. We speculate that TNF-a may play a role in the development of NEC by being an active member of an inflammatory cascade leading to the pathology associated with the disease.
Objective: The aim of this study was to determine whether administration of anti-TNF-a reduces the incidence and severity of NEC.
Methods: Newborn neonatal rats were fed milk formula and exposed to asphyxia and cold stress twice daily to develop NEC. The pups were divided into two experimental groups: those injected i.p. with 5 mg/kg anti-mouse monoclonal TNF-a once per day for three days (NEC+anti-TNF-a) and those sham injected with saline (NEC). After 96 hours, animals were sacrificed and the number of TNF-a positive cells in the liver and the histologic NEC score were evaluated in the anti-TNF-a injected animals compared to the sham injected animals.
Results: The administration of 5 mg/kg/day of anti-mouse monoclonal TNF-a significantly reduced the amount of TNF-a positive Kupffer cells in the liver of neonatal rats. This specific neutralization of hepatic TNF-a production significantly decreased the incidence and severity of experimental NEC (p<0.01). Conclusions: Neutralization of hepatic TNF-a production reduces the incidence and severity of NEC. This finding suggests a possible therapy for the treatment of this disease.
Supported by the NIH Grants HD-39657 and HD-47237 (to B.D)
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Saunders, T., Halpern, M., Clark, J. et al. 102 Effect of Anti-TNF-A Treatment on the Incidence of Experimental Necrotizing Enterocolitis. Pediatr Res 58, 372 (2005). https://doi.org/10.1203/00006450-200508000-00131
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DOI: https://doi.org/10.1203/00006450-200508000-00131
