HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/4/G757    most recent 00408.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (16) Citing Articles via Google Scholar Google Scholar Articles by Halpern, M. D. Articles by Dvorak, B. Search for Related Content PubMed PubMed Citation Articles by Halpern, M. D. Articles by Dvorak, B.

INFLAMMATION/IMMUNITY/MEDIATORS

Reduction of experimental necrotizing enterocolitis with anti-TNF-

¹Department of Pediatrics and Steele Children’s Research Center and ²Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona

Submitted 31 August 2005 ; accepted in final form 31 October 2005

Necrotizing enterocolitis (NEC) is the most common gastrointestinal disease of premature infants. However, despite significant morbidity and mortality, the etiology and pathogenesis of NEC are poorly understood. Evidence suggests that ileal proinflammatory mediators such as IL-18 contribute to the pathology associated with this disease. In addition, we have previously shown that upregulation of TNF- in the liver is correlated with ileal disease severity in a neonatal rat model of NEC. With the use of a neonatal rat model of NEC, we evaluated the incidence and severity of ileal damage along with the production of both hepatic and ileal proinflammatory cytokines in animals injected with (anti-TNF-; n = 23) or without (NEC; n = 25) a monoclonal anti-TNF- antibody. In addition, we assessed changes in apoptosis and ileal permeability in the NEC and anti-TNF- groups. Ileal damage was significantly decreased, and the incidence of NEC was reduced from 80% to 17% in animals receiving anti-TNF-. Hepatic TNF- and hepatic and ileal IL-18 were significantly decreased in pups given anti-TNF- compared with those sham injected. In addition, ileal luminal levels of both TNF- and IL-18 were significantly decreased in the anti-TNF--injected group. Ileal paracellular permeability and the proapoptotic markers Bax and cleaved caspase-3 were significantly decreased in the anti-TNF- group. These data show that hepatic TNF- is an important component for the development of NEC in the neonatal rat model and suggest that anti-TNF- could be used as a potential therapy for human NEC.

tumor necrosis factor-; anti-tumor necrosis factor-; proinflammatory cytokines; liver/gut axis

This article has been cited by other articles:

				A. Maheshwari, A. R. Kurundkar, S. S. Shaik, D. R. Kelly, Y. Hartman, W. Zhang, R. Dimmitt, S. Saeed, D. A. Randolph, C. Aprahamian, et al. Epithelial cells in fetal intestine produce chemerin to recruit macrophages Am J Physiol Gastrointest Liver Physiol, July 1, 2009; 297(1): G1 - G10. [Abstract] [Full Text] [PDF]

				G Henderson, S Craig, R J Baier, N Helps, P Brocklehurst, and W McGuire Cytokine gene polymorphisms in preterm infants with necrotising enterocolitis: genetic association study Arch. Dis. Child. Fetal Neonatal Ed., March 1, 2009; 94(2): F124 - F128. [Abstract] [Full Text] [PDF]

				C. Sodhi, W. Richardson, S. Gribar, and D. J. Hackam The development of animal models for the study of necrotizing enterocolitis Dis. Model. Mech., September 1, 2008; 1(2-3): 94 - 98. [Abstract] [Full Text] [PDF]

				M. D. Halpern, L. Khailova, D. Molla-Hosseini, K. Arganbright, C. Reynolds, M. Yajima, J. Hoshiba, and B. Dvorak Decreased development of necrotizing enterocolitis in IL-18-deficient mice Am J Physiol Gastrointest Liver Physiol, January 1, 2008; 294(1): G20 - G26. [Abstract] [Full Text] [PDF]