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Intestinal alkaline phosphatase administration in newborns decreases systemic inflammatory cytokine expression in a neonatal necrotizing enterocolitis rat model. J Surg Res 2012 Oct;177(2):228-34 PMID: 22687880 PMCID: PMC5664150

Pubmed ID

22687880

DOI

10.1016/j.jss.2012.05.039

Abstract

BACKGROUND: Supplementation of intestinal alkaline phosphatase (IAP), an endogenous protein expressed in the intestines, decreases the severity of necrotizing enterocolitis (NEC)-associated intestinal injury and permeability. We hypothesized that IAP administration is protective in a dose-dependent manner of the inflammatory response in a neonatal rat model.

MATERIALS AND METHODS: Pre- and full-term newborn Sprague-Dawley rat pups were sacrificed on day of life 3. Control pups were vaginally delivered and dam fed. Preterm pups were delivered via cesarean section and exposed to intermittent hypoxia and formula feeds containing lipopolysaccharide (NEC) with and without IAP. Three different standardized doses were administered to a group of pups treated with 40, 4, and 0.4U/kg of bovine IAP (NEC+IAP40, IAP4, or IAP0.4U). Reverse transcription-real-time polymerase chain reaction (RT-PCR) for inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α on liver and lung tissues and serum cytokine analysis for interleukin (IL)-1β, IL-6, IL-10, and TNF-α were performed. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests, expressed as mean±standard error of the mean and P≤0.05 considered significant.

RESULTS: Levels of cytokines IL-1β, IL-6, and TNF-α increased significantly in NEC versus control, returning to control levels with increasing doses of supplemental enteral IAP. Hepatic and pulmonary TNF-α and iNOS messenger ribonucleic acid expressions increased in NEC, and the remaining elevated despite IAP supplementation.

CONCLUSIONS: Proinflammatory cytokine expression is increased systemically with intestinal NEC injury. Administration of IAP significantly reduces systemic proinflammatory cytokine expression in a dose-dependent manner. Early supplemental enteral IAP may reduce NEC-related injury and be useful for reducing effects caused by a proinflammatory cascade.

Author List

Rentea RM, Liedel JL, Fredrich K, Welak SR, Pritchard KA Jr, Oldham KT, Simpson PM, Gourlay DM

Authors

David M. Gourlay MD Chief, Professor in the Surgery department at Medical College of Wisconsin
Keith T. Oldham MD Professor in the Surgery department at Medical College of Wisconsin
Kirkwood A. Pritchard PhD Professor in the Surgery department at Medical College of Wisconsin
Pippa M. Simpson PhD Chief, Professor in the Pediatrics department at Medical College of Wisconsin
Scott R. Welak MD Assistant Professor in the Pediatrics department at Medical College of Wisconsin




Scopus

2-s2.0-84866042288   8 Citations

MESH terms used to index this publication - Major topics in bold

Alkaline Phosphatase
Animals
Animals, Newborn
Cytokines
Drug Evaluation, Preclinical
Enterocolitis, Necrotizing
Female
Hepatitis
Pneumonia
Pregnancy
Rats
Rats, Sprague-Dawley
jenkins-FCD Prod-310 bff9d975ec7f2d302586822146c2801dd4449aad