Shogo Seo1, Hiromu Miyake2, Mashriq Alganabi3, Maarten Janssen Lok3, Joshua S O'Connell3, Carol Lee3, Bo Li3, Agostino Pierro4. 1. Division of General and Thoracic Surgery, Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatric General and Urogenital Surgery, Juntendo University School of Medicine, Tokyo, Japan. 2. Division of General and Thoracic Surgery, Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada; Department of Pediatric Surgery, Shizuoka Children's Hospital, Shizuoka, Japan. 3. Division of General and Thoracic Surgery, Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada. 4. Division of General and Thoracic Surgery, Translational Medicine Program, The Hospital for Sick Children, Toronto, Ontario, Canada. Electronic address: agostino.pierro@sickkids.ca.
Abstract
BACKGROUND AND PURPOSE: Excessive inflammatory cell infiltration and accumulation in the intestinal mucosa are pathological features of necrotizing enterocolitis (NEC) leading to intestinal barrier disruption. Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory agent that regulates intestinal epithelial barrier homeostasis. We previously demonstrated that VIP-ergic neuron expression is decreased in experimental NEC ileum, and this may be associated with inflammation and barrier compromise. We hypothesize that exogenous VIP administration has a beneficial effect in NEC. METHODS: NEC was induced in C57BL/6 mice by gavage feeding, hypoxia, and lipopolysaccharide administration between postnatal day (P) 5 and 9. There were four studied groups: Control (n = 6): Breast feeding without stress factors; Control + VIP (n = 5): Breast feeding + intraperitoneal VIP injection once a day from P5 to P9; NEC (n = 9): mice exposed to NEC induction; NEC + VIP (n = 9): NEC induction + intraperitoneal VIP injection. Terminal ileum was harvested on P9. NEC severity, intestinal inflammation, (IL-6 and TNFα), and Tight junctions (Claudin-3) were evaluated. RESULTS: NEC severity and intestinal inflammation were significantly decreased in NEC + VIP compared to NEC. Tight junction expression was significantly increased in NEC + VIP compared to NEC. CONCLUSION: VIP administration has a beneficial therapeutic effect in NEC by reducing inflammation and tight junction disruption.
BACKGROUND AND PURPOSE: Excessive inflammatory cell infiltration and accumulation in the intestinal mucosa are pathological features of necrotizing enterocolitis (NEC) leading to intestinal barrier disruption. Vasoactive intestinal peptide (VIP) is a potent anti-inflammatory agent that regulates intestinal epithelial barrier homeostasis. We previously demonstrated that VIP-ergic neuron expression is decreased in experimental NEC ileum, and this may be associated with inflammation and barrier compromise. We hypothesize that exogenous VIP administration has a beneficial effect in NEC. METHODS:NEC was induced in C57BL/6 mice by gavage feeding, hypoxia, and lipopolysaccharide administration between postnatal day (P) 5 and 9. There were four studied groups: Control (n = 6): Breast feeding without stress factors; Control + VIP (n = 5): Breast feeding + intraperitoneal VIP injection once a day from P5 to P9; NEC (n = 9): mice exposed to NEC induction; NEC + VIP (n = 9): NEC induction + intraperitoneal VIP injection. Terminal ileum was harvested on P9. NEC severity, intestinal inflammation, (IL-6 and TNFα), and Tight junctions (Claudin-3) were evaluated. RESULTS:NEC severity and intestinal inflammation were significantly decreased in NEC + VIP compared to NEC. Tight junction expression was significantly increased in NEC + VIP compared to NEC. CONCLUSION:VIP administration has a beneficial therapeutic effect in NEC by reducing inflammation and tight junction disruption.