BACKGROUND: Necrotizing enterocolitis (NEC) is the most common surgical emergency in neonates, with an incidence of 0.5-2.4 cases per 1000 live births and a mortality rate between 10% and 50%. Neonates affected by NEC develop a septic injury that is associated with increased risk of neurological impairment due to intraventricular bleeding and chronic lung disease. Intestinal alkaline phosphatase (IAP) is an endogenous protein that has been shown to inactivate the endotoxin lipopolysaccharide (LPS), and has recently been used successfully as an adjunct to treat sepsis in adult patients. We tested the hypothesis that systemic, exogenous IAP will mitigate the inflammatory response as measured by serum levels of proinflammatory cytokines in a rat model of NEC. METHODS: Newborn Sprague-Dawley rats were divided into groups. Control pups were dam fed. NEC was induced by feeding formula containing LPS and exposure to intermittent hypoxia. NEC pups were given intraperitoneal injections of 4 or 40 glycine units (U) of IAP or placebo twice daily. Intestine and serum was collected for cytokine analysis as well as measurement of alkaline phosphatase activity. RESULTS: Systemic IAP administration significantly increased serum alkaline phosphatase activity in a dose- and time-dependent fashion. The proinflammatory cytokines tumor necrosis factor α, interleukin 6, and interleukin 1β were significantly increased in NEC rats versus controls on days 2 and 3. Importantly, treatment with 40 U systemic IAP decreased these proinflammatory cytokines back to near-control levels. CONCLUSIONS: Systemic IAP administration appears effective in mitigating the systemic inflammatory response associated with NEC, and may prove to be a valuable adjunctive treatment for NEC.
BACKGROUND:Necrotizing enterocolitis (NEC) is the most common surgical emergency in neonates, with an incidence of 0.5-2.4 cases per 1000 live births and a mortality rate between 10% and 50%. Neonates affected by NEC develop a septic injury that is associated with increased risk of neurological impairment due to intraventricular bleeding and chronic lung disease. Intestinal alkaline phosphatase (IAP) is an endogenous protein that has been shown to inactivate the endotoxin lipopolysaccharide (LPS), and has recently been used successfully as an adjunct to treat sepsis in adult patients. We tested the hypothesis that systemic, exogenous IAP will mitigate the inflammatory response as measured by serum levels of proinflammatory cytokines in a rat model of NEC. METHODS: Newborn Sprague-Dawley rats were divided into groups. Control pups were dam fed. NEC was induced by feeding formula containing LPS and exposure to intermittent hypoxia. NEC pups were given intraperitoneal injections of 4 or 40 glycine units (U) of IAP or placebo twice daily. Intestine and serum was collected for cytokine analysis as well as measurement of alkaline phosphatase activity. RESULTS: Systemic IAP administration significantly increased serum alkaline phosphatase activity in a dose- and time-dependent fashion. The proinflammatory cytokines tumor necrosis factor α, interleukin 6, and interleukin 1β were significantly increased in NEC rats versus controls on days 2 and 3. Importantly, treatment with 40 U systemic IAP decreased these proinflammatory cytokines back to near-control levels. CONCLUSIONS: Systemic IAP administration appears effective in mitigating the systemic inflammatory response associated with NEC, and may prove to be a valuable adjunctive treatment for NEC.
Authors: Farzad Ebrahimi; Madhu S Malo; Sayeda Nasrin Alam; Angela K Moss; Halim Yammine; Sundaram Ramasamy; Brishti Biswas; Kathryn T Chen; Nur Muhammad; Golam Mostafa; H Shaw Warren; Elizabeth L Hohmann; Richard A Hodin Journal: J Gastrointest Surg Date: 2011-03-01 Impact factor: 3.452
Authors: Claudia N Emami; Nikunj Chokshi; Jin Wang; Catherine Hunter; Yigit Guner; Kerstin Goth; Larry Wang; Anatoly Grishin; Henri R Ford Journal: Am J Surg Date: 2012-04 Impact factor: 2.565
Authors: Cynthia L Leaphart; Jaime Cavallo; Steven C Gribar; Selma Cetin; Jun Li; Maria F Branca; Theresa D Dubowski; Chhinder P Sodhi; David J Hackam Journal: J Immunol Date: 2007-10-01 Impact factor: 5.422
Authors: Ben E Biesterveld; Shannon M Koehler; Nathan P Heinzerling; Rebecca M Rentea; Katherine Fredrich; Scott R Welak; David M Gourlay Journal: J Surg Res Date: 2015-02-19 Impact factor: 2.192
Authors: Nathan P Heinzerling; Jennifer L Liedel; Scott R Welak; Katherine Fredrich; Ben E Biesterveld; Kirkwood A Pritchard; David M Gourlay Journal: J Pediatr Surg Date: 2014-01-31 Impact factor: 2.545
Authors: Ramazan Yildiz; Mahmut Ok; Merve Ider; Ugur Aydogdu; Amir Naseri; Kurtulus Parlak; Erdem Gulersoy Journal: J Vet Res Date: 2018-12-10 Impact factor: 1.744
Authors: Alva Presbitero; Emiliano Mancini; Ruud Brands; Valeria V Krzhizhanovskaya; Peter M A Sloot Journal: Front Immunol Date: 2018-10-11 Impact factor: 7.561