Langenbeck's Archives of Surgery

, Volume 389, Issue 5, pp 341–349 | Cite as

Current concept of pathophysiological understanding and natural course of ulcerative colitis

Current Concepts in Clinical Surgery

Abstract

Introduction

According to the current paradigm both ulcerative colitis (UC) and Crohn’s disease (CD) result from a complex interplay of genetic susceptibility factors, environmental factors, alterations of the physiological intestinal flora and a defective regulation of the intestinal immune system.

Discussion

The objective of this review is to give an overview of these factors and mechanisms, including genetic, environmental and microbial factors, with special alterations of relevant cellular components of the intestinal immune system such as T cells, macrophages and epithelial cells will then be addressed. In addition, the most relevant animal model systems that have contributed to our current pathogenetic understanding will be introduced. Clinically, the natural course of UC with special reference to the risk of colorectal cancer will be addressed.

Conclusion

The elucidation of pathomechanisms at the level of the intestinal immune system provides the potential for novel, effective treatment strategies. Best surgical management of patients with UC, however, still remains a challenge.

Keyword

Ulcerative colitis 

References

  1. 1.
    Orholm M, et al (1991) Familial occurrence of inflammatory bowel disease. N Engl J Med 324:84–88PubMedGoogle Scholar
  2. 2.
    Satsangi J, et al (1996) Contribution of genes of the major histocompatibility complex to susceptibility and disease phenotype in inflammatory bowel disease. Lancet 347:1212–1217PubMedGoogle Scholar
  3. 3.
    Futami S, et al (1995) HLA-DRB1*1502 allele, subtype of DR15, is associated with susceptibility to ulcerative colitis and its progression. Dig Dis Sci 40:814–818PubMedGoogle Scholar
  4. 4.
    Orchard TR, et al (2000) Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease. Gastroenterology 118:274–278PubMedGoogle Scholar
  5. 5.
    Saxon A, et al (1990) A distinct subset of antineutrophil cytoplasmic antibodies is associated with inflammatory bowel disease. J Allergy Clin Immunol 86:202–210PubMedGoogle Scholar
  6. 6.
    Duerr RH, et al (1991) Anti-neutrophil cytoplasmic antibodies in ulcerative colitis. Comparison with other colitides/diarrheal illnesses. Gastroenterology 100:1590–1596PubMedGoogle Scholar
  7. 7.
    Sandborn WJ, et al (1995) Antineutrophil cytoplasmic antibody correlates with chronic pouchitis after ileal pouch–anal anastomosis. Am J Gastroenterol 90:740–747PubMedGoogle Scholar
  8. 8.
    Sandborn WJ, et al (1996) Association of antineutrophil cytoplasmic antibodies with resistance to treatment of left-sided ulcerative colitis: results of a pilot study. Mayo Clin Proc 71:431–436PubMedGoogle Scholar
  9. 9.
    Papo M, et al (1996) Antineutrophil cytoplasmic antibodies in relatives of patients with inflammatory bowel disease. Am J Gastroenterol 91:1512–1515PubMedGoogle Scholar
  10. 10.
    Cohavy O, et al (2000) Colonic bacteria express an ulcerative colitis pANCA-related protein epitope. Infect Immun 68:1542–1548CrossRefPubMedGoogle Scholar
  11. 11.
    Bhagat S, Das KM (1994) A shared and unique peptide in the human colon, eye, and joint detected by a monoclonal antibody. Gastroenterology 107:103–108PubMedGoogle Scholar
  12. 12.
    Vashishtha A, Fischetti VA (1993) Surface-exposed conserved region of the streptococcal M protein induces antibodies cross-reactive with denatured forms of myosin. J Immunol 150:4693–4701PubMedGoogle Scholar
  13. 13.
    Thomas GA, et al (2000) Role of smoking in inflammatory bowel disease: implications for therapy. Postgrad Med J 76:273–279CrossRefPubMedGoogle Scholar
  14. 14.
    Lindberg E, et al (1988) Smoking and inflammatory bowel disease. A case control study. Gut 29:352–357PubMedGoogle Scholar
  15. 15.
    Miller LG, et al (1982) Reversible alterations in immunoregulatory T cells in smoking. Analysis by monoclonal antibodies and flow cytometry. Chest 82:526–529PubMedGoogle Scholar
  16. 16.
    Srivastava ED, et al (1991) Smoking, humoral immunity, and ulcerative colitis. Gut 32:1016–1019PubMedGoogle Scholar
  17. 17.
    Cope GF, Heatley RV, Kelleher JK (1986) Smoking and colonic mucus in ulcerative colitis. BMJ 293:481Google Scholar
  18. 18.
    Sher ME, et al (1999) The influence of cigarette smoking on cytokine levels in patients with inflammatory bowel disease. Inflamm Bowel Dis 5:73–78PubMedGoogle Scholar
  19. 19.
    Madretsma S, et al (1996) In-vivo effect of nicotine on cytokine production by human non-adherent mononuclear cells. Eur J Gastroenterol Hepatol 8:1017–1020PubMedGoogle Scholar
  20. 20.
    Evans JM, et al (1997) Non-steroidal anti-inflammatory drugs are associated with emergency admission to hospital for colitis due to inflammatory bowel disease. Gut 40:619–622PubMedGoogle Scholar
  21. 21.
    McCartney SA, et al (1999) Selective COX-2 inhibitors and human inflammatory bowel disease. Aliment Pharmacol Ther 13:1115–1117PubMedGoogle Scholar
  22. 22.
    Herbert TB, Cohen S (1993) Stress and immunity in humans: a meta-analytic review. Psychosom Med 55:364–379PubMedGoogle Scholar
  23. 23.
    Levenstein S, et al (2000) Stress and exacerbation in ulcerative colitis: a prospective study of patients enrolled in remission. Am J Gastroenterol 95:1213–1220CrossRefPubMedGoogle Scholar
  24. 24.
    Madara JL, et al (1985) Characterization of spontaneous colitis in cotton-top tamarins (Saguinus oedipus) and its response to sulfasalazine. Gastroenterology 88:13–19PubMedGoogle Scholar
  25. 25.
    Rutgeerts P, et al (1994) Appendectomy protects against ulcerative colitis. Gastroenterology 106:1251–1253PubMedGoogle Scholar
  26. 26.
    Andersson RE, et al (2001) Appendectomy and protection against ulcerative colitis. N Engl J Med 344:808–814CrossRefPubMedGoogle Scholar
  27. 27.
    Okazaki K, et al (2000) A patient with improvement of ulcerative colitis after appendectomy. Gastroenterology 119:502–506PubMedGoogle Scholar
  28. 28.
    Mizoguchi A, et al (1996) Role of appendix in the development of inflammatory bowel disease in TCR-alpha mutant mice. J Exp Med 184:707–715PubMedGoogle Scholar
  29. 29.
    Sartor RB, (1997) Role of the enteric microflora in the pathogenesis of intestinal inflammation and arthritis (review). Aliment Pharmacol Ther 11 [Suppl 3]:17–22, discussion 22–23Google Scholar
  30. 30.
    Burke DA, Axon AT (1988) Adhesive Escherichia coli in inflammatory bowel disease and infective diarrhoea. BMJ 297:102–104PubMedGoogle Scholar
  31. 31.
    Walmsley RS, et al (1998) Absence of Escherichia coli, Listeria monocytogenes, and Klebsiella pneumoniae antigens within inflammatory bowel disease tissues. J Clin Pathol 51:657–661PubMedGoogle Scholar
  32. 32.
    Shanahan F (2000) Mechanisms of immunologic sensation of intestinal contents. Am J Physiol 278:G191–G196Google Scholar
  33. 33.
    D’Haens GR, et al (1998) Early lesions of recurrent Crohn’s disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology 114:262–267PubMedGoogle Scholar
  34. 34.
    Sartor RB (1998) Postoperative recurrence of Crohn’s disease: the enemy is within the fecal stream. Gastroenterology 114:398–407PubMedGoogle Scholar
  35. 35.
    Turunen UM, et al (1998) Long-term treatment of ulcerative colitis with ciprofloxacin: a prospective, double-blind, placebo-controlled study. Gastroenterology 115:1072–1078PubMedGoogle Scholar
  36. 36.
    Shen B, et al (2001) A randomized clinical trial of ciprofloxacin and metronidazole to treat acute pouchitis. Inflamm Bowel Dis 7:301–305CrossRefPubMedGoogle Scholar
  37. 37.
    Rembacken BJ, et al (1999) Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 354:635–639PubMedGoogle Scholar
  38. 38.
    Kruis W, Fric P, Stolte M (2001) Maintenance of remission in ulcerative colitis is equally effective with Escherichia coli Nissle 1917 and standard mesalamine. Gastroenterology 120:A127 [Suppl]Google Scholar
  39. 39.
    Gionchetti P, et al (2000) Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 119:305–309PubMedGoogle Scholar
  40. 40.
    Qiao L, et al (1991) Activation and signaling status of human lamina propria T lymphocytes. Gastroenterology 101:1529–1536PubMedGoogle Scholar
  41. 41.
    Targan SR, et al (1995) Definition of a lamina propria T cell responsive state. Enhanced cytokine responsiveness of T cells stimulated through the CD2 pathway. J Immunol 154:664–675PubMedGoogle Scholar
  42. 42.
    Braunstein J, et al (1997) T cells of the human intestinal lamina propria are high producers of interleukin-10. Gut 41:215–220PubMedGoogle Scholar
  43. 43.
    Boirivant M, et al (1996) Stimulated human lamina propria T cells manifest enhanced Fas-mediated apoptosis. J Clin Invest 98:2616–2622PubMedGoogle Scholar
  44. 44.
    Ayabe T, et al (1997) A pilot study of centrifugal leukocyte apheresis for corticosteroid-resistant active ulcerative colitis. Intern Med 36:322–326PubMedGoogle Scholar
  45. 45.
    Hanai H, et al (2002) Granulocyte and monocyte adsorption apheresis in patients with severe corticosteroid unresponsive ulcerative colitis. Gastroenterol T1187:A-431Google Scholar
  46. 46.
    Kawamura N, et al (2002) Efficacy of leucocyte apheresis with the use of nonwoven polyester filter in ulcerative colitis. Gastroenterol T1196:A-431Google Scholar
  47. 47.
    Stumbles P, Mc William A, Holt P (1999) Dendritic cells and mucosal macrophages. In: Ogra PL, Bienenstock I, Strober W (eds) Mucosal immunology. Academic Press, San DiegoGoogle Scholar
  48. 48.
    Casini-Raggi V, et al (1995) Mucosal imbalance of IL-1 and IL-1 receptor antagonist in inflammatory bowel disease. A novel mechanism of chronic intestinal inflammation. J Immunol 154:2434–2440PubMedGoogle Scholar
  49. 49.
    Monteleone G, et al (1997) Interleukin 12 is expressed and actively released by Crohn’s disease intestinal lamina propria mononuclear cells. Gastroenterology 112:1169–1178PubMedGoogle Scholar
  50. 50.
    Christ AD, et al (1998) An interleukin 12-related cytokine is up-regulated in ulcerative colitis but not in Crohn’s disease. Gastroenterology 115:307–313PubMedGoogle Scholar
  51. 51.
    Auphan N, et al (1995) Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science 270:286–290PubMedGoogle Scholar
  52. 52.
    Weber CK, et al (2000) Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology 119:1209–1218PubMedGoogle Scholar
  53. 53.
    Dubuquoy L, et al (2003) Impaired expression of peroxisome proliferator-activated receptor gamma in ulcerative colitis. Gastroenterology 124:1265–1276CrossRefPubMedGoogle Scholar
  54. 54.
    Lewis JD, et al (2001) An open-label trial of the PPAR-gamma ligand rosiglitazone for active ulcerative colitis. Am J Gastroenterol 96:3323–3328CrossRefPubMedGoogle Scholar
  55. 55.
    Autschbach F, et al (1995) Cytokine messenger RNA expression and proliferation status of intestinal mononuclear cells in noninflamed gut and Crohn’s disease. Virchows Arch 426:51–60PubMedGoogle Scholar
  56. 56.
    Watanabe M, et al (1995) Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes. J Clin Invest 95:2945–2953PubMedGoogle Scholar
  57. 57.
    Elson CO, et al (1995) Experimental models of inflammatory bowel disease. Gastroenterology 109:1344–1367PubMedGoogle Scholar
  58. 58.
    Boirivant M, et al (1998) Oxazolone colitis: a murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. J Exp Med 188Google Scholar
  59. 59.
    Mombaerts P, et al (1993) Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell 75:274–282PubMedGoogle Scholar
  60. 60.
    Sadlack B, et al (1993) Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 75:253–261PubMedGoogle Scholar
  61. 61.
    Watanabe M, et al (1995) Interleukin 7 is produced by human intestinal epithelial cells and regulates the proliferation of intestinal mucosal lymphocytes. Clin Invest 95:2945–2953PubMedGoogle Scholar
  62. 62.
    Heller F, et al (2002) Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity 17:629–638PubMedGoogle Scholar
  63. 63.
    Mizoguchi E, et al (1997) Antineutrophil cytoplasmic antibodies in T-cell receptor alpha-deficient mice with chronic colitis. Gastroenterology 113:1828–1835PubMedGoogle Scholar
  64. 64.
    Lichtiger S, et al (1994) Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med 330:1841–1845CrossRefPubMedGoogle Scholar
  65. 65.
    Watanabe M, et al (1998) Interleukin 7 transgenic mice develop chronic colitis with decreased interleukin 7 protein accumulation in the colonic mucosa. J Exp Med 187:389–402CrossRefPubMedGoogle Scholar
  66. 66.
    Holtmann MH, Galle PR (2003) Therapy-refractory and fulminant, toxic colitis. Dig Surg 20:372–374Google Scholar
  67. 67.
    Mourelle M, et al (1995) Induction of nitric oxide synthase in colonic smooth muscle from patients with toxic megacolon. Gastroenterology 109:1497PubMedGoogle Scholar
  68. 68.
    Mourelle M, et al (1996) Toxic dilatation of colon in a rat model of colitis is linked to an inducible form of nitric oxide synthase. Am J Physiol 33:G425Google Scholar
  69. 69.
    Caprilli R, et al (1987) Early recognition of toxic megacolon. J Clin Gastroenterol 9:136Google Scholar
  70. 70.
    Strauss RJ, et al (1976) The surgical management of toxic dilatation of the colon: a report of 28 cases and a review of the literature. Ann Surg 184:682PubMedGoogle Scholar
  71. 71.
    Danovitch SH (1989) Fulminant colitis and toxic megacolon. Gastroenterol Clin North Am 18:73PubMedGoogle Scholar
  72. 72.
    Hendrikson C, Kreiner S, Binder V (1985) Long term prognosis in ulcerative colitis—based on results from a regional patient group from the country of Copenhagen. Gut 26:158–163PubMedGoogle Scholar
  73. 73.
    Langholz E, Munkholm P, Davidson M (1994) Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology 107:3–11PubMedGoogle Scholar
  74. 74.
    Bernstein CN, et al (2001) Cancer risk in patients with inflammatory bowel disease. Cancer 48:526–535Google Scholar
  75. 75.
    Eaden JA, Abrams KR, Mayberry JF (2001) The risk of colorectal cancer in ulcerative colitis. a meta-analysis. Gut 48:526–535CrossRefPubMedGoogle Scholar
  76. 76.
    Loftus EV (2003) Does monitoring prevent cancer in inflammatory bowel disease? J Clin Gastroenterol 36[Suppl 1]:S79–S83Google Scholar
  77. 77.
    Schlemper RJ, et al (2000) The Vienna classification of gastrointestinal epithelial neoplasia. Gut 47:251–255PubMedGoogle Scholar
  78. 78.
    Riddell RH, et al (1983) Dysplasia in inflammatory bowel disease. Standardized classification with provisional clinical applications. Hum Pathol 14:931–968PubMedGoogle Scholar
  79. 79.
    Blackstone MO, et al (1981) Dysplasia-associated lesion or mass (DALM) detected by colonoscopy in long-standing ulcerative colitis: an indication for colectomy. Gastroenterology 80:366–374PubMedGoogle Scholar
  80. 80.
    Bernstein CN, Shanahan F, Weinstein WM (1994) Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis? Lancet 343:71–74PubMedGoogle Scholar
  81. 81.
    Provenzale D, Onken J (2001) Surveillance issues in inflammatory bowel disease: ulcerative colitis. J Clin Gastroenterol 32:99–105CrossRefPubMedGoogle Scholar
  82. 82.
    Tanaka S, et al (2000) Detailed colonoscopy for detecting early superficial carcinoma; recent developments. J Gastroenterol 35 [Suppl 12]:121–125Google Scholar
  83. 83.
    Kiesslich R, et al (2003) Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis. Gastroenterology 124:880–888PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Department of MedicineJohannes Gutenberg UniversityMainzGermany

Personalised recommendations