Oral Administration of Surfactant Protein-A Reduces Pathology in an Experimental Model of Necrotizing Enterocolitis. Issue 5 (May 2015)

• Record Type: Journal Article
• Authors: Quintanilla, Hector D.; Liu, Yuying; Fatheree, Nicole Y.; Atkins, Constance L.; Hashmi, Syed S.; Floros, Joanna; McCormack, Francis X.; Rhoads, Jon Marc; Alcorn, Joseph L.
• Is Part Of: Journal of pediatric gastroenterology and nutrition. Volume 60:Issue 5(2015)
• Publication Date: 2015-05
• Subjects: immunomodulation -- NEC -- proinflammatory cytokines -- SP-A -- TLR4; Children -- Nutrition -- Periodicals; Pediatric gastroenterology -- Periodicals; Infants -- Nutrition -- Periodicals; Nutrition disorders in children -- Periodicals; Child Nutrition -- Periodicals; Digestive System -- growth & development -- Periodicals; Gastrointestinal Diseases -- Periodicals; Infant Nutrition -- Periodicals; Nutrition Disorders -- Periodicals; Child; 618.923
• DOI: 10.1097/MPG.0000000000000678
• Languages: English
• ISSNs: 0277-2116

Abstract

Abstract: Objectives: Necrotizing enterocolitis (NEC) frequently results in significant morbidity and mortality in premature infants. Others reported that mice deficient in pulmonary surfactant protein-A (SP-A) born and raised in a nonhygienic environment succumb to significant gastrointestinal tract pathology, and enteral administration of purified SP-A significantly reduced mortality. We hypothesized that oral administration of purified SP-A can ameliorate pathology in an experimental model of neonatal NEC. Methods: Experimental NEC was induced in newborn Sprague–Dawley rat pups by daily formula gavage and intermittent exposure to hypoxia. Purified human SP-A (5 μg/day) was administered by oral gavage. After 4 days, surviving pups were sacrificed, and intestinal pathology was assessed by histological examination of distal terminal ileal sections. Intestinal levels of inflammatory cytokines (IL-1β, IFN-γ, and TNF-α) were assessed by enzyme-linked immunosorbent assay and levels of Toll-like receptor 4 (TLR4) by Western analysis. Results: Sixty-one percent of the gavaged rat pups that survived to day 4 met the criteria for experimental NEC after hypoxia, whereas treatment with SP-A significantly reduced mortality and assessment of NEC. Intestinal levels of proinflammatory cytokines were significantly increased in pups exposed to hypoxia. Administration of SP-A to pups exposed to hypoxia significantly reduced IL-1β and TNF-α levels, but had little effect on elevated levels of IFN-γ. SP-A treatment of hypoxia-exposed pups significantly reduced expression of intestinal TLR4, key in NEC pathogenesis. Conclusions: In a rat model of experimental neonatal NEC, oral administration of SP-A reduces intestinal levels of proinflammatory cytokines and TLR4 protein and ameliorates adverse outcomes associated with gastrointestinal pathologies.