Seminars in Fetal & Neonatal Medicine
Volume 11, Issue 5 , Pages 369-377 , October 2006

Intestinal immune defences and the inflammatory response in necrotising enterocolitis

  • Camilia R. Martin

      Affiliations

    • Harvard Medical School, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Rose-318, Boston, MA 02215, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 617 667 3276; fax: +1 617 667 7040.
    • ,
  • W. Allan Walker

      Affiliations

    • Combined Program in Pediatric Gastroenterology and Nutrition at Harvard Medical School, Massachusetts General Hospital, 114 16th Street, Charlestown, MA 02129, USA

References 

  1. Hintz SR, Kendrick DE, Stoll BJ, et al. Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis. Pediatrics. 2005;115:696–703
  2. Simon NP. Follow-up for infants with necrotizing enterocolitis. Clin Perinatol. 1994;21:411–424
  3. Stoll BJ. Epidemiology of necrotizing enterocolitis. Clin Perinatol. 1994;21:205–218
  4. Lemons JA, Bauer CR, Oh W, et al. Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 through December 1996. NICHD Neonatal Research Network. Pediatrics. 2001;107:E1
  5. Caplan M, Jilling T. The pathophysiology of necrotizing enterocolitis. NeoReviews. 2001;2:c103–c108
  6. Walker WA. Development of the intestinal mucosal barrier. J Pediatr Gastroenterol Nutr. 2002;34(Suppl. 1):S33–S39
  7. Forchielli ML, Walker WA. The effect of protective nutrients on mucosal defense in the immature intestine. Acta Paediatr Suppl. 2005;94:74–83
  8. Claud EC, Walker WA. Hypothesis: inappropriate colonization of the premature intestine can cause neonatal necrotizing enterocolitis. FASEB J. 2001;15:1398–1403
  9. Fusunyan RD, Nanthakumar NN, Baldeon ME, Walker WA. Evidence for an innate immune response in the immature human intestine: toll-like receptors on fetal enterocytes. Pediatr Res. 2001;49:589–593
  10. Claud EC, Lu L, Anton PM, Savidge T, Walker WA, Cherayil BJ. Developmentally regulated IkappaB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation. Proc Natl Acad Sci USA. 2004;101:7404–7408
  11. Nanthakumar NN, Walker WA. Personal communication, 2005.
  12. Caplan MS, MacKendrick W. Inflammatory mediators and intestinal injury. Clin Perinatol. 1994;21:235–246
  13. Hsueh W, Gonzalez-Crussi F. Ischemic bowel necrosis induced by platelet-activating factor: an experimental model. Methods Achiev Exp Pathol. 1988;13:208–239
  14. Ewer AK, Al-Salti W, Coney AM, Marshall JM, Ramani P, Booth IW. The role of platelet activating factor in a neonatal piglet model of necrotising enterocolitis. Gut. 2004;53:207–213
  15. Hsueh W, Gonzalez-Crussi F, Arroyave JL. Platelet-activating factor: an endogenous mediator for bowel necrosis in endotoxemia. FASEB J. 1987;1:403–405
  16. Caplan MS, Sun XM, Hsueh W. Hypoxia causes ischemic bowel necrosis in rats: the role of platelet-activating factor (PAF-acether). Gastroenterology. 1990;99:979–986
  17. Llausas-Magana E, Hsueh W, Arroyave CM, Arroyave JL, Torre-Amione G, Gonzalez-Crussi F. Cobra venom factor, an activator of the complement system, enhances the bowel necrosis induced by platelet-activating factor. Immunopharmacology. 1988;15:31–37
  18. Hsueh W, Caplan MS, Sun X, Tan X, MacKendrick W, Gonzalez-Crussi F. Platelet-activating factor, tumor necrosis factor, hypoxia and necrotizing enterocolitis. Acta Paediatr Suppl. 1994;396:11–17
  19. Rabinowitz SS, Dzakpasu P, Piecuch S, Leblanc P, Valencia G, Kornecki E. Platelet-activating factor in infants at risk for necrotizing enterocolitis. J Pediatr. 2001;138:81–86
  20. Caplan MS, Sun XM, Hseuh W, Hageman JR. Role of platelet activating factor and tumor necrosis factor-alpha in neonatal necrotizing enterocolitis. J Pediatr. 1990;116:960–964
  21. Amer MD, Hedlund E, Rochester J, Caplan MS. Platelet-activating factor concentration in the stool of human newborns: effects of enteral feeding and neonatal necrotizing enterocolitis. Biol Neonate. 2004;85:159–166
  22. MacKendrick W, Hill N, Hsueh W, Caplan M. Increase in plasma platelet-activating factor levels in enterally fed preterm infants. Biol Neonate. 1993;64:89–95
  23. Birk D, Berger D, Limmer J, Beger HG. Is the elimination of endotoxin and cytokines with continuous lavage an alternative procedure in necrotizing enterocolitis?. Acta Paediatr Suppl. 1994;396:24–26
  24. Viscardi RM, Lyon NH, Sun CC, Hebel JR, Hasday JD. Inflammatory cytokine mRNAs in surgical specimens of necrotizing enterocolitis and normal newborn intestine. Pediatr Pathol Lab Med. 1997;17:547–559
  25. Pender SL, Braegger C, Gunther U, et al. Matrix metalloproteinases in necrotising enterocolitis. Pediatr Res. 2003;54:160–164
  26. Tan X, Hsueh W, Gonzalez-Crussi F. Cellular localization of tumor necrosis factor (TNF)-alpha transcripts in normal bowel and in necrotizing enterocolitis. TNF gene expression by Paneth cells, intestinal eosinophils, and macrophages. Am J Pathol. 1993;142:1858–1865
  27. Morecroft JA, Spitz L, Hamilton PA, Holmes SJ. Plasma cytokine levels in necrotizing enterocolitis. Acta Paediatr Suppl. 1994;396:18–20
  28. Harris MC, Costarino AT, Sullivan JS. Cytokine elevations in critically ill infants with sepsis and necrotizing enterocolitis. [see comments] J Pediatr. 1994;124:105–111
  29. Ren Y, Lin CL, Li Z, et al. Up-regulation of macrophage migration inhibitory factor in infants with acute neonatal necrotizing enterocolitis. Histopathology. 2005;46:659–667
  30. Duffy LC, Zielezny MA, Carrion V, et al. Concordance of bacterial cultures with endotoxin and interleukin-6 in necrotizing enterocolitis. Dig Dis Sci. 1997;42:359–365
  31. Halpern MD, Holubec H, Dominguez JA, et al. Up-regulation of IL-18 and IL-12 in the ileum of neonatal rats with necrotizing enterocolitis. Pediatr Res. 2002;51:733–739
  32. Nadler EP, Stanford A, Zhang XR. Intestinal cytokine gene expression in infants with acute necrotizing enterocolitis: interleukin-11 mRNA expression inversely correlates with extent of disease. J Pediatr Surg. 2001;36:1122–1129
  33. Edelson MB, Bagwell CE, Rozycki HJ. Circulating pro- and counterinflammatory cytokine levels and severity in necrotizing enterocolitis. Pediatrics. 1999;103:766–771
  34. Nanthakumar NN, Fusunyan RD, Sanderson I, Walker WA. Inflammation in the developing human intestine: a possible pathophysiologic contribution to necrotizing enterocolitis. Proc Natl Acad Sci USA. 2000;97:6043–6048
  35. Ballance WA, Dahms BB, Shenker N, Kliegman RM. Pathology of neonatal necrotizing enterocolitis: a ten-year experience. J Pediatr. 1990;117:S6–S13
  36. Bister V, Salmela MT, Heikkila P, et al. Matrilysins-1 and -2 (MMP-7 and -26) and metalloelastase (MMP-12), unlike MMP-19, are up-regulated in necrotizing enterocolitis. J Pediatr Gastroenterol Nutr. 2005;40:60–66
  37. Pender SL, Tickle SP, Docherty AJ, Howie D, Wathen NC, MacDonald TT. A major role for matrix metalloproteinases in T cell injury in the gut. J Immunol. 1997;158:1582–1590
  38. Caplan MS, Lickerman M, Adler L, Dietsch GN, Yu A. The role of recombinant platelet-activating factor acetylhydrolase in a neonatal rat model of necrotizing enterocolitis. Pediatr Res. 1997;42:779–783
  39. Muguruma K, Gray PW, Tjoelker LW, Johnston JM. The central role of PAF in necrotizing enterocolitis development. Adv Exp Med Biol. 1997;407:379–382
  40. Furukawa M, Lee EL, Johnston JM. Platelet-activating factor-induced ischemic bowel necrosis: the effect of platelet-activating factor acetylhydrolase. Pediatr Res. 1993;34:237–241
  41. Furukawa M, Narahara H, Yasuda K, Johnston JM. Presence of platelet-activating factor-acetylhydrolase in milk. J Lipid Res. 1993;34:1603–1609
  42. Caplan M, Hsueh W, Kelly A, Donovan M. Serum PAF acetylhydrolase increases during neonatal maturation. Prostaglandins. 1990;39:705–714
  43. Chheda S, Palkowetz KH, Garofalo R, Rassin DK, Goldman AS. Decreased interleukin-10 production by neonatal monocytes and T cells: relationship to decreased production and expression of tumor necrosis factor-alpha and its receptors. Pediatr Res. 1996;40:475–483
  44. Kotiranta-Ainamo A, Rautonen J, Rautonen N. Interleukin-10 production by cord blood mononuclear cells. Pediatr Res. 1997;41:110–113
  45. Le T, Leung L, Carroll WL, Schibler KR. Regulation of interleukin-10 gene expression: possible mechanisms accounting for its upregulation and for maturational differences in its expression by blood mononuclear cells. Blood. 1997;89:4112–4119
  46. Jones CA, Cayabyab RG, Kwong KY, et al. Undetectable interleukin (IL)-10 and persistent IL-8 expression early in hyaline membrane disease: a possible developmental basis for the predisposition to chronic lung inflammation in preterm newborns. Pediatr Res. 1996;39:966–975
  47. Steidler L, Hans W, Schotte L, et al. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science. 2000;289:1352–1355
  48. Ozturk H, Dokucu AI, Ogun C, Buyukbayram H. Protective effects of recombinant human interleukin-10 on intestines of hypoxia-induced necrotizing enterocolitis in immature rats. J Pediatr Surg. 2002;37:1330–1333
  49. Du X, Liu Q, Yang Z, et al. Protective effects of interleukin-11 in a murine model of ischemic bowel necrosis. Am J Physiol. 1997;272:G545–G552
  50. Dvorak B, Halpern MD, Holubec H, et al. Maternal milk reduces severity of necrotizing enterocolitis and increases intestinal IL-10 in a neonatal rat model. Pediatr Res. 2003;53:426–433
  51. Fituch CC, Palkowetz KH, Goldman AS, Schanler RJ. Concentrations of IL-10 in preterm human milk and in milk from mothers of infants with necrotizing enterocolitis. Acta Paediatr. 2004;93:1496–1500
  52. Claud EC, Savidge T, Walker WA. Modulation of human intestinal epithelial cell IL-8 secretion by human milk factors. Pediatr Res. 2003;53:419–425
  53. Ford H, Watkins S, Reblock K, Rowe M. The role of inflammatory cytokines and nitric oxide in the pathogenesis of necrotizing enterocolitis. J Pediatr Surg. 1997;32:275–282
  54. Miettinen PJ. Epidermal growth factor receptor in mice and men – any applications to clinical practice?. Ann Med. 1997;29:531–534
  55. Dvorak B, Halpern MD, Holubec H, et al. Epidermal growth factor reduces the development of necrotizing enterocolitis in a neonatal rat model. Am J Physiol Gastrointest Liver Physiol. 2002;282:G156–G164
  56. Halpern MD, Dominguez JA, Dvorakova K, et al. Ileal cytokine dysregulation in experimental necrotizing enterocolitis is reduced by epidermal growth factor. J Pediatr Gastroenterol Nutr. 2003;36:126–133
  57. Fagbemi AO, Wright N, Lakhoo K, Edwards AD. Immunoreactive epidermal growth factor receptors are present in gastrointestinal epithelial cells of preterm infants with necrotising enterocolitis. Early Hum Dev. 2001;65:1–9
  58. Shin CE, Falcone RA, Stuart L, Erwin CR, Warner BW. Diminished epidermal growth factor levels in infants with necrotizing enterocolitis. J Pediatr Surg. 2000;35:173–176discussion 7
  59. Treszl A, Kocsis I, Szathmari M, Schuler A, Tulassay T, Vasarhelyi B. Genetic variants of the tumour necrosis factor-alpha promoter gene do not influence the development of necrotizing enterocolitis. Acta Paediatr. 2001;90:1182–1185
  60. Treszl A, Heninger E, Kalman A, Schuler A, Tulassay T, Vasarhelyi B. Lower prevalence of IL-4 receptor alpha-chain gene G variant in very-low-birth-weight infants with necrotizing enterocolitis. J Pediatr Surg. 2003;38:1374–1378
  61. O'Neill LA. How NOD-ing off leads to Crohn disease. Nat Immunol. 2004;5:776–778
  62. Romero R, Gomez R, Ghezzi F, et al. A fetal systemic inflammatory response is followed by the spontaneous onset of preterm parturition. Am J Obstet Gynecol. 1998;179:186–193
  63. Yoon BH, Romero R, Kim KS, et al. A systemic fetal inflammatory response and the development of bronchopulmonary dysplasia. Am J Obstet Gynecol. 1999;181:773–779
  64. Yoon BH, Romero R, Park JS, et al. Fetal exposure to an intra-amniotic inflammation and the development of cerebral palsy at the age of three years. Am J Obstet Gynecol. 2000;182:675–681
  65. Yoon BH, Romero R, Yang SH, et al. Interleukin-6 concentrations in umbilical cord plasma are elevated in neonates with white matter lesions associated with periventricular leukomalacia. Am J Obstet Gynecol. 1996;174:1433–1440
  66. Leviton A, Paneth N, Reuss ML, et al. Maternal infection, fetal inflammatory response, and brain damage in very low birth weight infants. Developmental Epidemiology Network Investigators. Pediatr Res. 1999;46:566–575
  67. Gomez R, Romero R, Ghezzi F, Yoon BH, Mazor M, Berry SM. The fetal inflammatory response syndrome. Am J Obstet Gynecol. 1998;179:194–202
  68. Dammann O, Leviton A. Role of the fetus in perinatal infection and neonatal brain damage. Curr Opin Pediatr. 2000;12:99–104
  69. Martinez-Tallo E, Claure N, Bancalari E. Necrotizing enterocolitis in full-term or near-term infants: risk factors. Biol Neonate. 1997;71:292–298
  70. Uauy RD, Fanaroff AA, Korones SB, Phillips EA, Phillips JB, Wright LL. Necrotizing enterocolitis in very low birth weight infants: biodemographic and clinical correlates. National Institute of Child Health and Human Development Neonatal Research Network. J Pediatr. 1991;119:630–638
  71. Mercer BM, Miodovnik M, Thurnau GR, et al. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. J Am Med Assoc. 1997;278:989–995
  72. Kenyon S, Boulvain M, Neilson J. Antibiotics for preterm rupture of the membranes: a systematic review. Obstet Gynecol. 2004;104:1051–1057
  73. Kim YD, Hyun WY, Cha HJ. Funisitis and raised interleukin 6 concentrations in gastric aspirates at birth. Arch Dis Child Fetal Neonatal Ed. 2005;90:F349–F350
  74. Reber KM, Nankervis CA. Necrotizing enterocolitis: preventative strategies. Clin Perinatol. 2004;31:157–167
  75. Foster J, Cole M. Oral immunoglobulin for preventing necrotizing enterocolitis in preterm and low birth-weight neonates. Cochrane Database Syst Rev. 2004;(1):CD001816
  76. Bury RG, Tudehope D. Enteral antibiotics for preventing necrotizing enterocolitis in low birthweight or preterm infants. Cochrane Database Syst Rev. 2001;(1):CD000405
  77. Becker RM, Wu G, Galanko JA, et al. Reduced serum amino acid concentrations in infants with necrotizing enterocolitis. J Pediatr. 2000;137:785–793
  78. Amin HJ, Zamora SA, McMillan DD, et al. Arginine supplementation prevents necrotizing enterocolitis in the premature infant. J Pediatr. 2002;140:425–431

PII: S1744-165X(06)00030-8

doi: 10.1016/j.siny.2006.03.002

Seminars in Fetal & Neonatal Medicine
Volume 11, Issue 5 , Pages 369-377 , October 2006

Article Tools

* Image Usage & Resolution