New concepts of pathogenesis in IBD

  • C. Fiocchi
Chapter

Abstract

Inflammatory bowel disease (IBD) still remains an enigma and there is no real understanding of its etiology and pathogenesis. In spite of this, efforts directed at uncovering predisposing factors, identifying specific etiologic agents, creating new animal models, investigating immunologic abnormalities, and developing novel and more effective forms of therapy continue to expand. Until the cause and mechanism(s) of IBD are clearly understood there remain many implicated factors, as demonstrated by the variety of topics presented in the chapters of this book. To a large extent this reflects limitations in knowledge, even though there is general agreement that both Crohn’s disease (CD) and ulcerative colitis (UC) are intricate multifactorial entities. In the face of this discouraging complexity an in-depth discussion of IBD pathogenesis can be quite extensive and diffuse. This laborious approach has already been taken, and comprehensive reviews are available1,2. This chapter will instead focus on selected and recent developments, particularly those having an impact on the pathophysiology of IBD.

Keywords

Inflammatory Bowel Disease Ulcerative Colitis Intestinal Permeability Ulcerative Colitis Patient Chronic Intestinal Inflammation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Fiocchi C. Pathophysiology: facts, hopes and implications for treatment. In: Scholmerich J, Kruis W, Goebell H, Hohenberger W, Gross V, editors. Inflammatory bowel disease: pathophysiology as basis of treatment. Lancaster: Kluwer; 1993: 257–79.Google Scholar
  2. 2.
    Shanahan F. Pathogenesis of ulcerative colitis. Lancet. 1993; 342: 407–11.PubMedCrossRefGoogle Scholar
  3. 3.
    Sofaer J. Crohn’s disease: the genetic contribution. Gut. 1993; 34: 869–71.PubMedCrossRefGoogle Scholar
  4. 4.
    Lashner BA, Kirsner JB. The epidemiology of inflammatory bowel disease: are we learning anything new? Gastroenterology. 1992; 103: 696–8.PubMedGoogle Scholar
  5. 5.
    Asakura H, Tsuchiya M, Aiso S et al. Association of the human lymphocyte-DR2 antigen with Japanese ulcerative colitis. Gastroenterology. 1982; 82: 413–18.PubMedGoogle Scholar
  6. 6.
    Toyoda H, Wang S-J, Yang H-J et al. Distinct associations of HLA class II genes with inflammatory bowel disease. Gastroenterology. 1993; 104: 741–8.PubMedGoogle Scholar
  7. 7.
    Yang H, Rotter JI, Toyoda H et al. Ulcerative colitis: a genetically heterogeneous disorder defined by genetic (HLA class II) and subclinical (antineutrophil cytoplasmic antibodies) markers. J Clin Invest. 1993; 92: 1080–4.PubMedCrossRefGoogle Scholar
  8. 8.
    Fiocchi C, Roche JK, Michener WM. High prevalence of antibodies to intestinal epithelial antigens in patients with inflammatory bowel disease and their relatives. Ann Intern Med. 1989; 110: 786–94.PubMedGoogle Scholar
  9. 9.
    Saxon A, Shanahan F, Landers C, Ganz T, Targan S. A distinct subset of anti-neutrophil cytoplasmic antibodies is associated with inflammatory bowel disease. J Allergy Clin Immunol. 1990; 86: 202–10.PubMedCrossRefGoogle Scholar
  10. 10.
    Duerr RH, Targan SR, Landers CJ, Sutherland LR, Shanahan F. Anti-neutrophil cytoplasmic antibodies in ulcerative colitis. Comparison with other colitides/diarrheal diseases. Gastroenterology. 1991; 100: 1590–6.PubMedGoogle Scholar
  11. 11.
    Shanahan F, Duerr RH, Rotter JI et al. Neutrophil autoantibodies in ulcerative colitis: familial aggregation and genetic heterogeneity. Gastroenterology. 1992; 103: 456–61.PubMedGoogle Scholar
  12. 12.
    Dalekos GN, Manoussakis MN, Goussia AC, Tsianos EV, Moutsopoulos HM. Soluble interleukin-2 receptors, antineutrophil cytoplasmic antibodies, and other autoantibodies in patients with ulcerative colitis. Gut. 1993; 34: 658–64.PubMedCrossRefGoogle Scholar
  13. 13.
    Fiocchi C, Battisto JR, Farmer RG. Studies on isolated gut mucosal lymphocytes in inflammatory bowel disease. Detection of activated T cells and enhanced proliferation to Staphylococcus aureus and lipopolysaccharides. Dig Dis Sci. 1981; 26: 728–36.PubMedCrossRefGoogle Scholar
  14. 14.
    Pirzer U, Schonhaar A, Fleischer B, Hermann E, Buschenfelde K-HM. Reactivity of infiltration T lymphocytes with microbial antigens in Crohn’s disease. Lancet. 1991; 338: 1238–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Ibbotson JP, Lowes JR, Chahal H et al. Mucosal cell-mediated immunity to mycobacterial, enterobacterial and other microbial antigens in inflammatory bowel disease. Clin Exp Immunol. 1992; 87: 224–30.PubMedCrossRefGoogle Scholar
  16. 16.
    Szewczuk MR, Depew WT. Evidence for T lymphocyte reactivity to the 65 kilodalton heat shock protein of mycobacterium in active Crohn’s disease. Clin Invest Med. 1992; 15: 494–505.PubMedGoogle Scholar
  17. 17.
    Kruiningen HJV, Colombel JF, Cartun RW et al. An in-depth study of Crohn’s disease in two French families. Gastroenterology. 1993; 104: 351–60.PubMedGoogle Scholar
  18. 18.
    Wakefield AJ, Pittilo RM, Sim R et al. Evidence of persistent measles virus infection in Crohn’s disease. J Med Virol. 1993; 39: 345–53.PubMedCrossRefGoogle Scholar
  19. 19.
    Wakefield AJ, Sawyerr AM, Hudson M, Dhillon AP, Pounder RE. Smoking, the oral contraceptive pill, and Crohn’s disease. Dig Dis Sci. 1991; 36: 1147–50.PubMedCrossRefGoogle Scholar
  20. 20.
    Stenson WF. Animal models of inflammatory bowel disease. In Targan SR, Shanahan F, editors. Inflammatory bowel disease. From bench to bedside. Baltimore: Williams & Wilkins; 1994: 180–92.Google Scholar
  21. 21.
    Fiocchi C. Cytokines and animal models: a combined path to inflammatory bowel disease pathogenesis. Gastroenterology. 1993; 104: 1202–19.PubMedGoogle Scholar
  22. 22.
    Yamada T, Sartor RB, Marshall S, Specian RD, Grisham MB. Mucosal injury and inflammation in a model of chronic granulomatous colitis in rats. Gastroenterology. 1993; 104: 759–71.PubMedGoogle Scholar
  23. 23.
    McCall RD, Haskill S, Zimmermann EM, Lund PK, Thompson CR, Sartor RB. Tissue interleukin-1 and interleukin-1 receptor antagonist expression in enterocolitis in resistant and susceptible rats. Gastroenterology. 1994; 106: 960–72.PubMedGoogle Scholar
  24. 24.
    Cooper HS, Murthy SNS, Shah RS, Sedergran DJ. Clinicopathologic study of dextran sulfate sodium experimental murine colitis. Lab Invest. 1993; 69: 238–49.PubMedGoogle Scholar
  25. 25.
    Caplan MS, Hedlund E, Hill N, MacKendrick W. The role of endogenous nitric oxide and platelet-activating factor in hypoxia-induced intestinal injury in rats. Gastroenterology. 1994; 106: 346–52.PubMedGoogle Scholar
  26. 26.
    Rachmilewitz D, Stamler JS, Karmeli F et al. Peroxynitrite-induced rat colitis–a new model of colonic inflammation. Gastroenterology. 1994; 105: 1681–8.Google Scholar
  27. 27.
    Lacey SR, Lichtman S. Development of an animal model for ileoanal pouchitis. J Pediatr Surg. 1993; 28: 574–5.CrossRefGoogle Scholar
  28. 28.
    Bucy RP, Xu XY, Li J, Huang GQ. Cyclosporin A-induced autoimmune disease in mice. J Immunol. 1993; 154: 1039–50.Google Scholar
  29. 29.
    Powrie F, Leach MW, Mauze S, Cadde LB, Coffman RL. Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 seid mice. Int Immunol. 1993; 5: 1461–71.PubMedCrossRefGoogle Scholar
  30. 30.
    Morrisy PJ, Charrier K, Braddy S, Liggit D, Watson JD. CD4+ T cells that express high levels of CD45RB induce wasting disease when transferred into congenic severe combined immunodeficient mice. Disease development is prevented by cotransfer of purified CD4+ T cells. J Exp Med. 1993; 178: 237–44.CrossRefGoogle Scholar
  31. 31.
    Hammer RE, Maika SD, Richardson JA, Tang J-P, Taurog JD. Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human b2m: an animal model of HLA-B27-associated human disorders. Cell. 1990; 63: 1099–112.PubMedCrossRefGoogle Scholar
  32. 32.
    Sadlack B, Mertz H, Schorle H, Schimpl A, Feller AC, Horak I. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell. 1993; 75: 253–61.PubMedCrossRefGoogle Scholar
  33. 33.
    Kuhn R, Lohler J, Rennick D, Rajewsky K, Muller W. Interleukin-l0-deficient mice develop chronic enterocolitis. Cell. 1993; 75: 263–74.PubMedCrossRefGoogle Scholar
  34. 34.
    Mombaerts P, Mizoguchi E, Grusby MG, Glimcher LH, Bhan AK, Tonegawa S. Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell. 1993; 75: 275–82.CrossRefGoogle Scholar
  35. 35.
    Strober W, Ehrhardt RO. Chronic intestinal inflammation: an unexpected outcome in cytokine or T cell receptor mutant mice. Cell. 1993; 75: 203–5.PubMedCrossRefGoogle Scholar
  36. 36.
    Brandtzaeg P, Halstensen TS, Kett K. Immunopathology of inflammatory bowel disease. In: MacDermott RP, Stenson WF, editors. Inflammatory bowel disease. New York: Elsevier; 1992: 95–136.Google Scholar
  37. 37.
    Helgeland L, Tysk C, Jarnerot G et al. IgG subclass distribution in serum and rectal mucosa of monozygotic twins with or without inflammatory bowel disease. Gut. 1992; 33: 1358–64.PubMedCrossRefGoogle Scholar
  38. 38.
    Snook J. Are the inflammatory bowel diseases autoimmune disorders? Gut. 1990; 31: 9613.CrossRefGoogle Scholar
  39. 39.
    Das KM, Vecchi M, Sakamaki S. A shared and unique epitope(s) on human colon, skin, and biliary epithelium detected by a monoclonal antibody. Gastroenterology. 1990; 98: 464–9.PubMedGoogle Scholar
  40. 40.
    Halstensen TS, Das KM, Brandtzaeg P. Epithelial deposits of immunoglobulin GI and activated complement colocalise with the M r 40 kD putative autoantigen in ulcerative colitis. Gut. 1993; 34: 650–7.PubMedCrossRefGoogle Scholar
  41. 41.
    Das KM, Dasgupta A, Mandai A, Geng X. Autoimmunity to cytoskeletal protein tropomyosin. J Immunol. 1993; 150: 2487–93.PubMedGoogle Scholar
  42. 42.
    Mandal A, Dasgupta A, Jeffers L et al. Autoantibodies in sclerosing cholangitis against a shared peptide in biliary and colon epithelium. Gastroenterology. 1994; 106: 185–92.PubMedGoogle Scholar
  43. 43.
    Mayer L, Eisenhardt D. Lack of induction of suppressor T cells by intestinal epithelial cells from patients with inflammatory bowel disease. J Clin Invest. 1990; 86: 1255–60.PubMedCrossRefGoogle Scholar
  44. 44.
    Hoang P, Crotty B, Dalton HR, Jewell DP. Epithelial cells bearing class II molecules stimulate allogeneic human colonic intraepithelial lymphocytes. Gut. 1992; 33: 1089–93.PubMedCrossRefGoogle Scholar
  45. 45.
    Crotty B, Hoang P, Dalton HR, Jewell DP. Salicylates used in inflammatory bowel disease and colchicine impair interferon-y induced HLA-DR expression. Gut. 1992; 33: 59–64.PubMedCrossRefGoogle Scholar
  46. 46.
    Fiocchi C. Mucosal cellular immunity. In: Targan SR, Shanahan F, editors. Immunology and immunopathology of the liver and gastrointestinal tract. New York: Igaku-Shoin; 1990: 107–38.Google Scholar
  47. 47.
    Fukushima K, Masuda T, Ohtani H et al. Immunohistochemical characterization, distribution, and ultrastructure of lymphocytes bearing T-cell receptor γδ in inflammatory bowel disease. Gastroenterology. 1991; 101: 670–8.PubMedGoogle Scholar
  48. 48.
    Hoang P, Senju M, Lowes JR, Jewell DP. Phenotypic characterization of isolated intraepithelial lymphocytes in patients with ulcerative colitis and normal controls. Dig Dis Sci. 1992; 37: 1725–8.PubMedCrossRefGoogle Scholar
  49. 49.
    VanKerckhove C, Russell GJ, Deusch K et al. Oligoclonality of human intestinal intraepithelial T cells. J Exp Med. 1992; 175: 57–63.CrossRefGoogle Scholar
  50. 50.
    Landau SB, Balk SP, Yang L, Burke SK, Blumberg RS. T-cell receptor (TCR) γ variable region utilization is altered in ulcerative colitis. Gastroenterology. 1992; 102: A650.Google Scholar
  51. 51.
    Lionetti P, Breese E, Braegger CP, Murch SH, Taylor J, MacDonald TT. T-cell activation can induce either mucosal destruction or adaptation in cultured human fetal small intestine. Gastroenterology. 1993; 105: 373–81.PubMedGoogle Scholar
  52. 52.
    Qiao L, Schurmann G, Autschbach F, Wallich R, Meuer SC. Human intestinal mucosa alters T-cell reactivities. Gastroenterology. 1993; 105: 814–19.PubMedGoogle Scholar
  53. 53.
    Aisenberg J, Ebert EC, Mayer L. T-cell activation in human intestinal mucosa: the role of superantigens. Gastroenterology. 1993; 105: 1421–30.PubMedCrossRefGoogle Scholar
  54. 54.
    Posnett DN, Schmelkin I, Burton DA, August A, McGrath H, Mayer LF. T cell antigen receptor V gene usage. Increases in Vβ8+ T cells in Crohn’s disease. J Clin Invest. 1990; 85: 1770–6.PubMedCrossRefGoogle Scholar
  55. 55.
    Spencer J, Choy MY, MacDonald TT. T cell receptor Vβ expression by mucosal T cells. J Clin Pathol. 1991; 44: 915–18.PubMedCrossRefGoogle Scholar
  56. 56.
    Duchmann R, Strober W, Fiocchi C, James SP. TCR Vβ2 gene expression is selective in control but not in IBD lamina propria lymphocytes. Gastroenterology. 1992; 102: 617.Google Scholar
  57. 57.
    Paliard X, West SG, Lafferty JA et al. Evidence for the effects of a superantigen in rheumatoid arthritis. Science. 1991; 253: 325–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Sperber K, Ogata S, Sylvester C et al. A novel human macrophage-derived intestinal mucin secretagogue: implications for the pathogenesis of inflammatory bowel disease. Gastroenterology. 1993; 104: 1302–9.PubMedGoogle Scholar
  59. 59.
    Fox CC, Lichtenstein LM, Roche JK. Intestinal mast cell responses in idiopathic inflammatory bowel disease. Dig Dis Sci. 1993; 38: 1105–12.PubMedCrossRefGoogle Scholar
  60. 60.
    Martens MFWC, Huyben CMLC, Hendriks T. Collagen synthesis in fibroblasts from human colon: regulatory aspects and differences with skin fibroblasts. Gut. 1992; 33: 1664–70.PubMedCrossRefGoogle Scholar
  61. 61.
    Lee EY, Stesnson WF, DeChryver-Kecskemeti K. Thickening of muscularis mucosae in Crohn’s disease. Mod Pathol. 1991; 4: 87–90.PubMedGoogle Scholar
  62. 62.
    Vermillion DL, Huizinga JD, Riddell RH, Collins SM. Altered small intestinal smooth muscle function in Crohn’s disease. Gastroenterology. 1993; 104: 1692–9.PubMedGoogle Scholar
  63. 63.
    Strong SA, Klein JS, West GA, Fiocchi C. Activation of intestinal mesenchymal cells by IL1β induces inflammatory cytokine and procollagen gene expression. Gastroenterology. 1993; 104: A784.Google Scholar
  64. 64.
    Springer TA. Adhesion receptors of the immune system. Nature. 1990; 346: 425–34.PubMedCrossRefGoogle Scholar
  65. 65.
    Cronstein BC, Weissmann G. The adhesion molecules of inflammation. Arthritis Rheum. 1993; 36: 147–57.PubMedGoogle Scholar
  66. 66.
    Greenfield SM, Hamblin A, Punchard NA, Thompson RPH. Expression of adhesion molecules on circulating leucocytes in patients with inflammatory bowel disease. Clin Sci. 1992; 83: 221–6.PubMedGoogle Scholar
  67. 67.
    Malizia G, Calabrese A, Cottone M et al. Expression of leukocyte adhesion molecules by mucosal mononuclear phagocytes in inflammatory bowel disease. Gastroenterology. 1991; 100: 150–9.PubMedGoogle Scholar
  68. 68.
    Koizumi M, King N, Lobb R, Benjamin C, Podolsky DK. Expression of vascular adhesion molecules in inflammatory bowel disease. Gastroenterology. 1992; 103: 840–7.PubMedGoogle Scholar
  69. 69.
    Ohtani H, Nakamura S, Watanabe Y et al. Light and electron microscopic immunolocalization of endothelial leucocyte adhesion molecules-1 in inflammatory bowel disease. Virchows Arch A Pathol Anat. 1992; 420: 403–9.CrossRefGoogle Scholar
  70. 70.
    Nakamura S, Ohtani H, Watanabe Y et al. In situ expression of the cell adhesion molecules in inflammatory bowel disease. Lab Invest. 1993; 69: 77–85.PubMedGoogle Scholar
  71. 71.
    Mishra L, Mishra BB, Harris M, Bayless TM, Muchmore AV. In-vitro cell aggregation and cell adhesion molecules in Crohn’s disease. Gastroenterology. 1993; 104: 772–9.PubMedGoogle Scholar
  72. 72.
    Salmi M, Granfors K, MacDermott RP, Jalkanen S. Aberrant binding of lamina propria lymphocytes to vascular endothelium in inflammatory bowel disease. Gastroenterology. 1994; 106: 596–605.PubMedGoogle Scholar
  73. 73.
    Podolsky DK, Lobb R, King N et al. Attenuation of colitis in the cotton-top tamarin by anti-alpha 4 integrin monoclonal antibody. J Clin Invest. 1993; 92: 372–80.PubMedCrossRefGoogle Scholar
  74. 74.
    Oppenheim JJ, Neta R, Pathophysiological roles of cytokines in development, immunity, and inflammation. FASEB J. 1994; 8: 158–62.PubMedGoogle Scholar
  75. 75.
    Ferraris L, Karmeli F, Eliakim R, Klein J, Fiocchi C, Rachmilewitz D. Intestinal epithelial cells contribute to the enhanced generation of platelet activating factor in ulcerative colitis. Gut. 1993; 34: 665–8.PubMedCrossRefGoogle Scholar
  76. 76.
    Shannon VR, Stenson WF, Holtzman MJ. Induction of epithelial arachidonate 12lipoxygenase at active sites of inflammatory bowel disease. Am J Physiol. 1993; 264: G104–11.PubMedGoogle Scholar
  77. 77.
    Fiocchi C. Cytokines. In: MacDermott RP, Stenson W, editors. Inflammatory bowel disease. New York: Elsevier; 1992: 137–62.Google Scholar
  78. 78.
    Fiocchi C. Cytokines. In: Targan SR, Shanahan F, editors. Inflammatory bowel disease. From bench to bedside. Baltimore: Williams & Wilkins; 1994: 106–22.Google Scholar
  79. 79.
    Sartor RB. Cytokines in intestinal inflammation: pathophysiological and clinical considerations. Gastroenterology. 1994; 106: 533–9.PubMedGoogle Scholar
  80. 80.
    Podolsky DK, Fiocchi C. Cytokines and growth factors in inflammatory bowel disease. In: Kirsner JB, Shorter RG, editors. Inflammatory bowel disease. Lea & Febiger; 1995 ( In press ).Google Scholar
  81. 81.
    Sparano JA, Brandt LJ, Dutcher JP, DuBois JS, Atkins MB. Symptomatic exacerbation of Crohn disease after treatment with high-dose interleukin-2. Ann Intern Med. 1993; 118: 617–18.PubMedGoogle Scholar
  82. 82.
    James SP. Remission of Crohn’s disease after human immunodeficiency virus infection. Gastroenterology. 1988; 95: 1667–9.PubMedGoogle Scholar
  83. 83.
    Matsuura T, West GA, Klein JS et al Immune activation gene products are resistant to IL4 inhibitory activity in Crohn’s disease (CD). Gastroenterology. 1993; 194: A739.Google Scholar
  84. 84.
    Mullin GE, Lazenby AJ, Harris ML, Bayless TM, James SP. Increased interleukin-2 messenger RNA in the intestinal mucosal lesions of Crohn’s disease but not ulcerative colitis. Gastroenterology. 1992; 102: 1620–7.PubMedGoogle Scholar
  85. 85.
    Matsuura T, West GA, Klein JS, Ferraris L, Fiocchi C. Soluble interleukin 2, CD8 and CD4 receptors in inflammatory bowel disease. A comparative study of peripheral blood and intestinal mucosal levels. Gastroenterology. 1992; 102: 2006–14.PubMedGoogle Scholar
  86. 86.
    Arend WP. Interleukin-1 receptor antagonism. J Clin Invest. 1991; 88: 1445–51.PubMedCrossRefGoogle Scholar
  87. 87.
    Casini-Raggi V, Kam L, Jin Y, Fiocchi C, Pizarro TT, Cominelli F. Mucosal imbalance of interleukin-1 and interleukin-1 receptor antagonist in inflammatory bowel disease: a potential mechanism of chronic intestinal inflammation. 1994 (Submitted).Google Scholar
  88. 88.
    Mansfield JC, Holden H, Tarlow JK et al. Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist. Gastroenterology. 1994; 106: 637–42.PubMedGoogle Scholar
  89. 89.
    Hymas JS, Treem WR, Eddy E, Wyzga N, Moore RE. Tumor necrosis factor-α is not elevated in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr. 1991; 12: 233–6.CrossRefGoogle Scholar
  90. 90.
    Tan X, Hsueh W, Gonazles-Crussi F. Cellular localization of tumor necrosis factor (TNF-)-α transcripts in normal bowel and in necrotizing enterocolitis. Am J Pathol. 1993; 142: 1858–65.PubMedGoogle Scholar
  91. 91.
    Izzo RS, Witkon K, Chen AI, Hadjiyane C, Weinstein MI, Pellecchia C. Interleukin-8 and neutrophil markers in colonic mucosa from patients with ulcerative colitis. Am J Gastroenterol. 1992; 87: 1447–52.PubMedGoogle Scholar
  92. 92.
    Izzo RS, Witkon K, Chen AI, Hadjiyane C, Weinstein MI, Pellecchia C. Neutrophilactivating peptide (interleukin-8) in colonic mucosa from patients with Crohn’s disease. Scand J Gastroenterol. 1993; 28: 269–300.CrossRefGoogle Scholar
  93. 93.
    Mahida YR, Ceska M, Effenberger F, Kurlak L, Lindley I, Hawkey CJ. Enhanced synthesis of neutrophil-activating peptide-I/interleukin-8 in active ulcerative colitis. Clin Sci. 1992; 82: 273–5.PubMedGoogle Scholar
  94. 94.
    Eckmann L, Jung HC, Schurer-Maly C, Panja A, Morzycka-Wroblewska E, Kagnoff MF. Differential cytokine expression by human intestinal epithelial cell lines: regulated expression of interleukin 8. Gastroenterology. 1994; 105: 1689–97.Google Scholar
  95. 95.
    Zimmermann EM, Sartor RB, McCall RD, Pardo M, Bender D, Lund PK. Insulin growth factor I and interleukin lβ messenger RNA in a rat model of granulomatous enterocolitis and hepatitis. Gastroenterology. 1993; 105: 399–409.PubMedGoogle Scholar
  96. 96.
    Wright NA, Poulsom R, Stamp G et al. Trefoil peptide gene expression in gastrointestinal epithelial cells in inflammatory bowel disease. Gastroenterology. 1993; 194: 12–20.Google Scholar
  97. 97.
    Ohtani H, Nakamura S, Watanabe Y, Mizoi T, Saku T, Nagura H. Immunocytochemical localization of basic fibroblast growth factor in carcinomas and inflammatory lesions of the human digestive tract. Lab Invest. 1993; 68: 520–7.PubMedGoogle Scholar
  98. 98.
    Ciacci C, Lind SE, Podolsky DK. Transforming growth factor β regulation of migration in wounded rat intestinal epithelial monolayers. Gastroenterology. 1993; 105: 93–101.PubMedGoogle Scholar
  99. 99.
    Dignass AU, Podolsky DK. Cytokine modulation of intestinal epithelial cell restitution: central role of transforming growth factor β. Gastroenterology. 1993; 105: 1323–32.PubMedCrossRefGoogle Scholar
  100. 100.
    Goetzel EJ, Sreedharan SP. Mediators of communication and adaptation in the neuroendocrine and immune systems. FASEB J. 1992; 6: 2646–52.Google Scholar
  101. 101.
    Sternberg EM, Chrousos GP, Wilder RL, Gold PW. The stress response and the regulation of inflammatory disease. Ann Intern Med. 1992; 117: 854–66.PubMedGoogle Scholar
  102. 102.
    Geboes K, Rutgeerts P, Ectors N et al. Major histocompatibility class II expression on the small intestinal nervous system in Crohn’s disease. Gastroenterology. 1992; 103: 439–47.PubMedGoogle Scholar
  103. 103.
    Boirivant M, Fais S, Annibale B, Agostini D, Fave GD, Pallone F. Vasoactive intestinal polypeptide modulates the in vitro immunoglobulin A production by intestinal lamina propria lymphocytes. Gastroenterology. 1994; 106: 576–82.PubMedGoogle Scholar
  104. 104.
    Lloyd AR, Oppenheim JJ. Poly’s lament: the neglected role of the polymorphonuclear neutrophil in the afferent limb of the immune response. Immunol Today. 1992; 13.Google Scholar
  105. 105.
    Simmonds NJ, Rampton DS. Inflammatory bowel disease — a radical view. Gut. 1993; 34: 865–8.PubMedCrossRefGoogle Scholar
  106. 106.
    Oshitani N, Kitano A, Okabe H, Nakamura S, Matsumoto T, Kobayashi K. Location of superoxide anion generation in human colonic mucosa obtained by biopsy. Gut. 1993; 34: 936–8.PubMedCrossRefGoogle Scholar
  107. 107.
    Baldassano RN, Schreiber S, Johnston RB, Fu RD, Muraki T, MacDermott RP. Crohn’s disease monocytes are primed for accentuated release of toxic oxygen metabolites. Gastroenterology. 1993; 105: 60–6.PubMedGoogle Scholar
  108. 108.
    Bilotta J, Waye JD. Hydrogen peroxide enteritis: the ‘Snow White’ sign. Gastrointest Endosc. 1989; 35: 428–30.PubMedCrossRefGoogle Scholar
  109. 109.
    Tamai H, Levin S, Gaginella TS. Induction of colitis in rats by 2′-2′-azobis (2-amidinopropane) dihydrochloride. Inflammation. 1992; 16: 69–81.PubMedCrossRefGoogle Scholar
  110. 110.
    Williams JP. Phagocytes, toxic oxygen metabolites and inflammatory bowel disease: implications for treatment. Ann R Coll Surg Engl. 1990; 72: 253–62.PubMedGoogle Scholar
  111. 111.
    Rudra T, Motley RJ, Rhodes J. Does smoking improve colitis? Scand J Gastroenterol. 1989; l70 (Suppl.): 61–3.CrossRefGoogle Scholar
  112. 112.
    Cottone M, Rosselli M, Orlando A et al. Smoking habits and recurrence of Crohn’s disease. Gastroenterology. 1994; 106: 643–8.PubMedGoogle Scholar
  113. 113.
    Rhodes T, Thomas GAO. Smoking: good or bad for inflammatory bowel disease? Gastroenterology. 1994; 106: 807–10.PubMedGoogle Scholar
  114. 114.
    Pullman RD, Rhodes J, Ganesh S et al. Transdermal nicotine for active ulcerative colitis. N Engl J Med. 1994; 330: 811–15.CrossRefGoogle Scholar
  115. 115.
    Katz KD, Hollander D, Vadheim CM et al. Intestinal permeability in patients with Crohn’s disease and their healthy relatives. Gastroenterology. 1989; 97: 927–31.PubMedGoogle Scholar
  116. 116.
    Teahon K, Smethurst P, Levi AJ, Menzies IS, Bjarnason I. Intestinal permeability in patients with Crohn’s disease and their first degree relatives. Gut. 1992; 33: 320–3.PubMedCrossRefGoogle Scholar
  117. 117.
    Adenis A, Colombel J-F, Lecouffe P et al. Increased pulmonary and intestinal permeability in Crohn’s disease. Gut. 1992; 33: 678–82.PubMedCrossRefGoogle Scholar
  118. 118.
    Hollander D. Permeability in Crohn’s disease: altered barrier function in healthy relatives? Gastroenterology. 1993; 1993: 1848–73.Google Scholar
  119. 119.
    May GR, Sutherland LR, Meddings JB. Is small intestinal permeability really increased in relatives of patients with Crohn’s disease? Gastroenterology. 1993; 104: 1627–32.PubMedGoogle Scholar
  120. 120.
    Jewell DP, Campieri M, Jarnerot G, Modigliani R, Rask-Madsen J. New therapeutic modalities for inflammatory bowel disease. Gastroenterol Int. 1993; 6: 1–12.Google Scholar
  121. 121.
    Hawkey CJ, Mahida YR, Hawthorne AB. Therapeutic interventions in gastrointestinal disease based on an understanding of inflammatory mediators. Agents Actions. 1992 (Special Conference Issue):C22–5.Google Scholar
  122. 122.
    Stenson WF, Cort D, Rodgers J et al. Dietary supplementation with fish oil in ulcerative colitis. Ann Intern Med. 1992; 116: 609–14.PubMedGoogle Scholar
  123. 123.
    Sutherland LR, May GR, Shaffer EA. Sulfasalazine revisited: a meta-analysis of 5aminosalycylic acid in the treatment of ulcerative colitis. Ann Intern Med. 1993; 118: 5409.Google Scholar
  124. 124.
    Sandborn WJ, Tremaine WJ. Cyclosporine treatment of inflammatory bowel disease. Mayo Clin Proc. 1992; 67: 981–90.PubMedGoogle Scholar
  125. 125.
    Scheppach W, Sommer H, Kirchner T et al. Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology. 1992; 103: 51–6.PubMedGoogle Scholar
  126. 126.
    Breuer RI, Buto SK, Christ ML et al. Rectal irrigation with short-chain fatty acids for distal ulcerative colitis. Dig Dis Sci. 1991; 36: 185–7.PubMedCrossRefGoogle Scholar
  127. 127.
    Roediger WEW. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet. 1980; 2: 712–15.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers and Axcan Pharma, Inc. 1994

Authors and Affiliations

  • C. Fiocchi

There are no affiliations available

Personalised recommendations