New insights into the pathogenesis and treatment of necrotizing enterocolitis: Toll-like receptors and beyond

Department of Surgery, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15224, USA.
Pediatric Research (Impact Factor: 2.84). 03/2011; 69(3):183-8. DOI: 10.1203/PDR.0b013e3182093280
Source: PubMed

ABSTRACT Necrotizing enterocolitis (NEC) is the leading cause of death from gastrointestinal disease in the preterm infant. The dismal results of current treatment for NEC highlight the urgent need for greater understanding of the pathogenesis of this disease, and the importance of discovering novel, molecular-specific therapies for it. Current dogma indicates that NEC development reflects an abnormal response by the premature infant to the microbial flora that colonizes the gastrointestinal tract, although the mechanisms that mediate these abnormal bacterial-enterocyte interactions and the reasons for the particularly increased susceptibility of the premature infant to the development of NEC remain incompletely explained. Recent evidence has shed light on an emerging role for the Toll-like receptors (TLRs) of the innate immune system as central players in the pathways that signal in response to enteric bacteria resulting in the development of NEC. We now review recent advances in the field of NEC and identify several exciting potential avenues for novel treatments by focusing on abnormal TLR4 signaling in the premature intestine in the pathogenesis of NEC. In so doing, we seek to offer new hope to the patients and their families who are affected by this devastating disorder.

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Available from: Matthew D Neal, Aug 23, 2015
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    • "We [5] and others [6] have shown that the initial injury to the small intestine primarily involves the loss of epithelial villi through apoptosis, which subsequently leads to the development of necrosis, a process that is consistent yet only incompletely explained. Loss of the epithelial barrier through apoptosis permits the translocation of bacteria and other antigens that are present within the lumen of the intestine, and which must normally be appropriately shielded from the immune system of the premature host in order to prevent the exaggerated inflammatory response, that is, typical of intestinal inflammatory conditions such as NEC [7] [8]. In response to the loss of epithelial continuity (which may be reflective of primary apoptosis or the early events that migh culminate in apoptosis), a multipronged healing program is initiated. "
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