Seminars in Pediatric Surgery
Volume 14, Issue 3 , Pages 137-144 , August 2005

Intestinal innate immunity: How does it relate to the pathogenesis of necrotizing enterocolitis

  • Josef Neu, MD

      Affiliations

    • Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida
  • ,
  • Mike Chen, MD

      Affiliations

    • Department of Surgery, University of Florida College of Medicine, Gainesville, Florida
  • ,
  • Elizabeth Beierle, MD

      Affiliations

    • Department of Surgery, University of Florida College of Medicine, Gainesville, Florida
    • Corresponding Author InformationAddress reprint requests and correspondence: Elizabeth A. Beierle, MD, University of Florida College of Medicine, Division of Pediatric Surgery, 1600 SW Archer Road, Room N6-10, Gainesville, FL 32608

References 

  1. Neu J . Necrotizing enterocolitis: the search for a unifying pathogenic theory leading to prevention . Pediatr Clin North Am . 1996;43(2):409–432
  2. Heninger E , Treszl A , Kocsis I , et al.  Genetic variants of the interleukin-18 promoter region (-607) influence the course of necrotising enterocolitis in very low birth weight neonates . Eur J Pediatr . 2002;161(7):410–411
  3. Treszl A , Heninger E , Kalman A , et al.  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(9):1374–1378
  4. La Gamma EF , Browne LE . Feeding practices for infants weighing less than 1500 G at birth and the pathogenesis of necrotizing enterocolitis . Clin Perinatol . 1994;21(2):271–306
  5. Caplan MS , MacKendrick W . Necrotizing enterocolitis: a review of pathogenetic mechanisms and implications for prevention . Pediatr Pathol . 1993;13(3):357–369
  6. Simon GL , Gorbach SL . The human intestinal microflora . Dig Dis Sci . 1986;31:S147–S162
  7. Walker WA . Role of nutrients and bacterial colonization in the development of intestinal host defense . J Pediatr Gastroenterol Nutr . 2000;30(suppl 2):S2–S7
  8. Goldman AS , Ogra PL . Anti-infectious and infectious agents in human milk . In:  Ogra PL ,  Mestecky J ,  Lamm ME , et al. editor. Mucosal Immunology (vol 1) . San Diego, CA: Academic Press; 1999;p. 72–85
  9. Mellander L , Carlsson B , Jalil F , et al.  Secretory IgA antibody response against Escherichia coli antigens in infants in relation to exposure . J Pediatr . 1985;107:430–433
  10. Goldblum RM , Ahlstedt S , Carlsson B , et al.  Antibody forming cells in human colostrum after oral immunisation . Nature . 1975;257:797–799
  11. Kleinman RE , Walker WA . The enteromammary immune system: an important new concept in breast milk host defense . Dig Dis Sci . 1979;24(11):876–882
  12. Ozturk H , Dokucu AI , Ogun C , et al.  Protective effects of recombinant human interleukin-10 on intestines of hypoxia-induced necrotizing enterocolitis in immature rats . J Pediatr Surg . 2002;37(9):1330–1333
  13. Fituch CC , Palkowetz KH , Goldman AS , et al.  Concentrations of IL-10 in preterm human milk and in milk from mothers of infants with necrotizing enterocolitis . Acta Paediatr . 2004;93(11):1496–1500
  14. 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(3):426–433
  15. Dinsmore JE , Jackson RJ , Smith SD . The protective role of gastric acidity in neonatal bacterial translocation . J Pediatr Surg . 1997;32(7):1014–1016
  16. Lebenthal E , Lee PC . Development of functional response in human exocrine pancreas . Pediatrics . 1980;66:556–560
  17. Rubinstein E , Mark Z , Haspel J , et al.  Antibacterial activity of the pancreatic fluid . Gastroenterology . 1985;88:927–932
  18. Walker WA , Wu M , Isselbacher KJ , et al.  Intestinal uptake of macromolecules . IV. The effect of pancreatic duct ligation on the breakdown of antigen and antigen–antibody complexes on the intestinal surface. Gastroenterology . 1975;69(6):1223–1229
  19. Beck-Sague CM , Azimi P , Fonseca SN , et al.  Bloodstream infections in neonatal intensive care unit patients: results of a multicenter study . Pediatr Infect Dis J . 1994;13(12):1110–1116
  20. Basaran UN , Celayir S , Eray N , et al.  The effect of an H2-receptor antagonist on small-bowel colonization and bacterial translocation in newborn rats . Pediatr Surg Int . 1998;13(2-3):118–120
  21. Laboisse CL . Structure of gastrointestial mucins: searching for the Rosetta stone . Biochimie . 1986;68(5):611–617
  22. Clamp JR , Creeth JM . Some non-mucin components of mucus and their possible biologic roles . Ciba Found Symp . 1984;109:121–136
  23. Podolsky DK . Oligosaccharide structures of human colonic mucin . J Biol Chem . 1985;260(14):8262–8271
  24. Shub MD , Pang KY , Swann DA , et al.  Age-related changes in chemical composition and physical properties of mucus glycoproteins from rat small intestine . Biochem J . 1983;215(2):405–411
  25. Sherman P , Forstner J , Roomi N , et al.  Mucin depletion in the intestine of malnourished rats . Am J Physiol . 1985;284(4 Pt 1):G418–G423
  26. Cheng H , Leblond CP . Origin, differentiation and renewal of the four main epithelial cell types in the mouse small intestine . I. Columnar cell. II. Mucus cell. III. Entero-endocrine cells. IV. Paneth cells. Am J Anat . 1974;141:461–536
  27. Mosely RL , Whetsell M , Klein JR . Proliferative properties of murine intestinal intraepithelial lymphocytes (IEL): IEL expressing TCR alpha beta or TCR tau delta are largely unresponsive to proliferative signals mediated via conventional stimulation of the CD3-TCR complex . Int Immunol . 1991;3:563–569
  28. Guy-Grand D , Cuenod-Jabri B , Malassis-Seris M , et al.  Complexity of the mouse gut T cell immune system: identification of two distinct natural killer T cell intraepithelial lineages . Eur J Immunol . 1996;26:2248–2256
  29. Beagley KW , Fujihashi K , Lagoo AS , et al.  Differences in intraepithelial lymphocyte T cell subsets isolated from murine small versus large intestine . J Immunol . 1995;154:5611–5619
  30. Denker BM , Nigam SK . Molecular structure and assembly of the tight junction . Am J Physiol . 1998;274:F1–F9
  31. Madara JL , Dharmsathaphorn K . Occluding junction structure-function relationships in a cultured epithelial monolayer . J Cell Biol . 1985;101:2124–2133
  32. Atsook K , Madara JL . An oligopeptide permeates intestinal tight junctions at glucose-elicited dilatations . Implications for oligopeptide absorption. Gastroenterology . 1991;100:719–724
  33. Venkatraman A , Ramakrishna BS , Pulimood AB . Butyrate hastens restoration of barrier function after thermal and detergent injury to rat distal colon in vitro . Scand J Gastroenterol . 1999;34(11):1087–1092
  34. Neu J , DeMarco V , Li N . Glutamine: clinical applications and mechanisms of action . Curr Opin Clin Nutr Metab Care . 2002;5(1):69–75
  35. Gebert A , Rothkotter HJ , Pabst R . M cells in Peyer's patches of the intestine . Int Rev Cytol . 1996;167:91–159
  36. Koldovsky O , Sunshine P , Kretchmer N . Cellular migration of intestinal epithelia in suckling and weaned rats . Nature . 1966;212(68):1389–1390
  37. Cetin S , Ford HR , Sysko LR , et al.  Endotoxin inhibits intestinal epithelial restitution through activation of Rho-GTPase and increased focal adhesions . J Biol Chem . 2004;279(23):24592–24600
  38. Steinman RM . The dendritic cell system and its role in immunogenicity . Annu Rev Immunol . 1991;9:271–296
  39. Cornes JC . Number, size and distribution of Peyer's patches in the human small intestine . Gut . 1965;6:225–233
  40. Metcalfe DD , Kaliner M , Dolon MA . The mast cell . CRC Crit Rev Immunol . 1981;3:23–74
  41. Conley ME , Delacroix DL . Intravascular and mucosal immunoglobulin A: two separate but related systems of immune defense? . Ann Intern Med . 1987;106:892–899
  42. Williams RC , Gibbons RJ . Inhibition of bacterial adherence by secretory immunoglobulin A . A mechanism of antigen disposal. Science . 1972;177:697–699
  43. Akira S , Taga T , Kishimoto T . Interleukin-6 in biology and medicine . Adv Immunol . 1993;54:1–78
  44. Tan X , Hsueh W , Gonzales-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
  45. Baggiolini M , Dewald B , Moser B . Human chemokines: an update . Ann Rev Immunol . 1997;15:675–705
  46. Okamoto SI , Mukaida N , Murakami S , et al.  Tumor necrosis factor alpha and interferon gamma synergistically induce interleukin 8 production in a human gastric cancer cell line through acting concurrently on AP-1 and NF-kappa B-like binding sites of the interleukin 8 gene . J Biol Chem . 1992;267:22506–22511
  47. Kurokowa M , Lynch K , Poldolsky DK . Effects of growth factors on an intestinal epithelial cell line: transforming growth factor beta inhibits proliferation and stimulates differentiation . Biochem Biophys Res Commun . 1987;142:775–782
  48. Park JH , MuCuster RH , Vanderhoof JA , et al.  Secretion of insulin-like growth factor-II(IGF-II) and IGF-binding protein-2 by intestinal epithelial (IEC-6) cells: implications for autocrine growth regulation . Endocrinology . 1992;131:1359–1368
  49. Sarna SK . Cyclic motor activity; migrating motor complex: 1985 . Gastroenterology . 1985;89(4):894–913
  50. Berseth CL . Gestational evolution of small intestine motility in preterm and term infants . J Pediatr . 1989;115(4):646–651
  51. Berseth CL . Gastrointestinal motility in the neonate . Clin Perinatol . 1996;23(2):179–190
  52. Milla PJ . Intestinal motility during ontogeny and intestinal pseudo-obstruction in children . Pediatr Clin North Am . 1996;43:511–532
  53. Hooper LV , Stappenbeck TS , Hong CV , et al.  Angiogenins: a new class of microbicidal proteins involved in innate immunity . Nat Immunol . 2003;4(3):269–273
  54. Hooper LV . Bacterial contributions to mammalian gut development . Trends Microbiol . 2004;12(3):129–134
  55. Stappenbeck TS , Hooper LV , Gordon JI . Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells . Proc Natl Acad Sci U S A . 2002;99(24):15451–15455
  56. Rakoff-Nahoum S , Paglino J , Eslami-Varzaneh F , et al.  Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis . Cell . 2004;118(2):229–241
  57. Takeda K , Kaisho T , Akira S . Toll-like receptors . Annu Rev Immunol . 2003;21:335–376
  58. Bourlioux P , Koletzko B , Guarner F , et al.  The intestine and its microflora are partners for the protection of the host: report on the Danone Symposium “The Intelligent Intestine,” held in Paris, June 14, 2002 . Am J Clin Nutr . 2003;78(4):675–683
  59. Saavedra JM . Clinical applications of probiotic agents . Am J Clin Nutr . 2001;73(6):1147S–1151S
  60. Daig R , Andus T , Aschenbrenner E , et al.  Increased interleukin 8 expression in the colon mucosa of patients with inflammatory bowel disease . Gut . 1996;38:216–222
  61. Sansonetti PJ , Arondel J , Huerre M , et al.  Interleukin-8 controls bacterial transepithelial translocation at the cost of epithelial destruction in experimental shigellosis . Infect Immun . 1999;67:1471–1480
  62. De Dooy J , Mahieu L , Van Bever H . The role of inflammation in the development of chronic lung disease in neonates . Eur J Pediatr . 2001;160(8):457–463
  63. Tauscher M , Berg D , Brockmann M , et al.  Association of histologic chorioamnionitis, increased levels of cord blood cytokines, and intracerebral hemorrhage in preterm neonates . Biol Neonate . 2003;83(3):166–170
  64. Yoon B , Park C , Chaiworapongsa T . Intrauterine infection and the development of cerebral palsy . BJOG . 2003;110(suppl 20):124–127
  65. 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(3):675–681
  66. Shalak L , Laptook A , Jafri H , et al.  Clinical chorioamnionitis, elevated cytokines, and brain injury in term infants . Pediatrics . 2002;110(4):673–680
  67. Kohse K , Carl A , Steinbach G . Whole blood interleukin-8 concentrations in capillary and cord blood of neonates for the diagnosis of systemic inflammatory states . Clin Lab . 2002;48(9-10):497–503
  68. Neish AS , Gewirtz AT , Zeng H , et al.  Prokaryotic regulation of epithelial responses by inhibition of IkappaB-alpha ubiquitination . Science . 2000;289(5484):1560–1563
  69. Nanthakumar NN , Fusunyan RD , Sanderson I , et al.  Inflammation in the developing human intestine: a possible pathophysiologic contribution to necrotizing enterocolitis . Proc Natl Acad Sci U S A . 2000;97(11):6043–6048
  70. Claud EC , Lu L , Anton PM , et al.  Developmentally regulated IkappaB expression in intestinal epithelium and susceptibility to flagellin-induced inflammation . Proc Natl Acad Sci U S A . 2004;101(19):7404–7408
  71. Kudsk KA , DeWitt RC , Tolley EA , et al.  Route and type of nutrition influence IgA-mediating intestinal cytokines . Ann Surg . 1999;229:662–667
  72. Kudsk KA . Current aspects of mucosal immunology and its influence by nutrition . Am J Surg . 2002;183(4):390–398
  73. Liboni K , Li N , Neu J . Mechanism of glutamine-mediated amelioration of lipopolysaccharide-induced IL-8 production in Caco-2 cells . Cytokine . 2004;26(2):57–65
  74. Li N , Liboni K , Fang MZ , et al.  Glutamine decreases lipopolysaccharide-induced intestinal inflammation in infant rats . Am J Physiol Gastrointest Liver Physiol . 2004;286(6):G914–G921
  75. Minekawa R , Takeda T , Sakata M , et al.  Human breast milk suppresses the transcriptional regulation of IL-1beta-induced NF-kappaB signaling in human intestinal cells . Am J Physiol Cell Physiol . 2004;287(5):C1404–C1411

PII: S1055-8586(05)00029-6

doi: 10.1053/j.sempedsurg.2005.05.001

Seminars in Pediatric Surgery
Volume 14, Issue 3 , Pages 137-144 , August 2005