Intestinal alkaline phosphatase prevents the systemic inflammatory response associated with necrotizing enterocolitis

Abstract

* Corresponding author. Division of General, Ave, Cincinnati, OH 45229. Tel.: þ513 803 16 E-mail address: sundeep.keswani@cchmc 0022-4804/$ e see front matter a 2013 Elsev http://dx.doi.org/10.1016/j.jss.2013.01.041 Necrotizing enterocolitis (NEC) represents a heterogeneous group of pathologic processes in the intestines of neonateswho are commonly premature with very low birth weights. It is characterized by an intense inflammatory response and has mortality ratesashighas20%e40% [1,2].Despite theestablished relationship between necrotizing enterocolitis and a proinflammatory cascade, thepathophysiology is still not completely understood.The involvementofenteral feedings, compromised intestinal perfusion, and bacterial invasion are commonly accepted factors [3]. Therehasbeensignificant research into the pathophysiology of NEC; however, there have been few major advances in its treatment. The mainstay of medical treatment continues to be stabilization with bowel rest, gastrointestinal decompression, parenteralnutrition, andantibiotics [4]. Further therapeutic strategies are much less well defined. Intestinal alkaline phosphatase (IAP) has been shown to be a promising pharmacologic target to reduce inflammation, with efficacy demonstrated in inflammatory bowel disease [5]. Multiple tissue-specific alkaline phosphatase isoforms have been described in humans, including intestinal, placental, and germ cell types. Within the intestine, IAP is localized to the brush border membrane and has been suggested to