Top

Langenbeck's Archives of Surgery

Published in:

01-10-2004 | Current Concepts in Clinical Surgery

Current concept of pathophysiological understanding and natural course of ulcerative colitis

Authors: Martin H. Holtmann, Peter R. Galle

Published in: Langenbeck's Archives of Surgery | Issue 5/2004

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.

Orholm M, et al (1991) Familial occurrence of inflammatory bowel disease. N Engl J Med 324:84–88PubMed

Satsangi J, et al (1996) Contribution of genes of the major histocompatibility complex to susceptibility and disease phenotype in inflammatory bowel disease. Lancet 347:1212–1217PubMed

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 40:814–818PubMed

Orchard TR, et al (2000) Clinical phenotype is related to HLA genotype in the peripheral arthropathies of inflammatory bowel disease. Gastroenterology 118:274–278PubMed

Saxon A, et al (1990) A distinct subset of antineutrophil cytoplasmic antibodies is associated with inflammatory bowel disease. J Allergy Clin Immunol 86:202–210PubMed

Duerr RH, et al (1991) Anti-neutrophil cytoplasmic antibodies in ulcerative colitis. Comparison with other colitides/diarrheal illnesses. Gastroenterology 100:1590–1596PubMed

Sandborn WJ, et al (1995) Antineutrophil cytoplasmic antibody correlates with chronic pouchitis after ileal pouch–anal anastomosis. Am J Gastroenterol 90:740–747PubMed

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 71:431–436PubMed

Papo M, et al (1996) Antineutrophil cytoplasmic antibodies in relatives of patients with inflammatory bowel disease. Am J Gastroenterol 91:1512–1515PubMed

10.

Cohavy O, et al (2000) Colonic bacteria express an ulcerative colitis pANCA-related protein epitope. Infect Immun 68:1542–1548CrossRefPubMed

11.

Bhagat S, Das KM (1994) A shared and unique peptide in the human colon, eye, and joint detected by a monoclonal antibody. Gastroenterology 107:103–108PubMed

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 150:4693–4701PubMed

13.

Thomas GA, et al (2000) Role of smoking in inflammatory bowel disease: implications for therapy. Postgrad Med J 76:273–279CrossRefPubMed

14.

Lindberg E, et al (1988) Smoking and inflammatory bowel disease. A case control study. Gut 29:352–357PubMed

15.

Miller LG, et al (1982) Reversible alterations in immunoregulatory T cells in smoking. Analysis by monoclonal antibodies and flow cytometry. Chest 82:526–529PubMed

16.

Srivastava ED, et al (1991) Smoking, humoral immunity, and ulcerative colitis. Gut 32:1016–1019PubMed

17.

Cope GF, Heatley RV, Kelleher JK (1986) Smoking and colonic mucus in ulcerative colitis. BMJ 293:481

18.

Sher ME, et al (1999) The influence of cigarette smoking on cytokine levels in patients with inflammatory bowel disease. Inflamm Bowel Dis 5:73–78PubMed

19.

Madretsma S, et al (1996) In-vivo effect of nicotine on cytokine production by human non-adherent mononuclear cells. Eur J Gastroenterol Hepatol 8:1017–1020PubMed

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 40:619–622PubMed

21.

McCartney SA, et al (1999) Selective COX-2 inhibitors and human inflammatory bowel disease. Aliment Pharmacol Ther 13:1115–1117PubMed

22.

Herbert TB, Cohen S (1993) Stress and immunity in humans: a meta-analytic review. Psychosom Med 55:364–379PubMed

23.

Levenstein S, et al (2000) Stress and exacerbation in ulcerative colitis: a prospective study of patients enrolled in remission. Am J Gastroenterol 95:1213–1220CrossRefPubMed

24.

Madara JL, et al (1985) Characterization of spontaneous colitis in cotton-top tamarins (Saguinus oedipus) and its response to sulfasalazine. Gastroenterology 88:13–19PubMed

25.

Rutgeerts P, et al (1994) Appendectomy protects against ulcerative colitis. Gastroenterology 106:1251–1253PubMed

26.

Andersson RE, et al (2001) Appendectomy and protection against ulcerative colitis. N Engl J Med 344:808–814CrossRefPubMed

27.

Okazaki K, et al (2000) A patient with improvement of ulcerative colitis after appendectomy. Gastroenterology 119:502–506PubMed

28.

Mizoguchi A, et al (1996) Role of appendix in the development of inflammatory bowel disease in TCR-alpha mutant mice. J Exp Med 184:707–715PubMed

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 22–23

30.

Burke DA, Axon AT (1988) Adhesive Escherichia coli in inflammatory bowel disease and infective diarrhoea. BMJ 297:102–104PubMed

31.

Walmsley RS, et al (1998) Absence of Escherichia coli, Listeria monocytogenes, and Klebsiella pneumoniae antigens within inflammatory bowel disease tissues. J Clin Pathol 51:657–661PubMed

32.

Shanahan F (2000) Mechanisms of immunologic sensation of intestinal contents. Am J Physiol 278:G191–G196

33.

D’Haens GR, et al (1998) Early lesions of recurrent Crohn’s disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology 114:262–267PubMed

34.

Sartor RB (1998) Postoperative recurrence of Crohn’s disease: the enemy is within the fecal stream. Gastroenterology 114:398–407PubMed

35.

Turunen UM, et al (1998) Long-term treatment of ulcerative colitis with ciprofloxacin: a prospective, double-blind, placebo-controlled study. Gastroenterology 115:1072–1078PubMed

36.

Shen B, et al (2001) A randomized clinical trial of ciprofloxacin and metronidazole to treat acute pouchitis. Inflamm Bowel Dis 7:301–305CrossRefPubMed

37.

Rembacken BJ, et al (1999) Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 354:635–639PubMed

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]

39.

Gionchetti P, et al (2000) Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 119:305–309PubMed

40.

Qiao L, et al (1991) Activation and signaling status of human lamina propria T lymphocytes. Gastroenterology 101:1529–1536PubMed

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 154:664–675PubMed

42.

Braunstein J, et al (1997) T cells of the human intestinal lamina propria are high producers of interleukin-10. Gut 41:215–220PubMed

43.

Boirivant M, et al (1996) Stimulated human lamina propria T cells manifest enhanced Fas-mediated apoptosis. J Clin Invest 98:2616–2622PubMed

44.

Ayabe T, et al (1997) A pilot study of centrifugal leukocyte apheresis for corticosteroid-resistant active ulcerative colitis. Intern Med 36:322–326PubMed

45.

Hanai H, et al (2002) Granulocyte and monocyte adsorption apheresis in patients with severe corticosteroid unresponsive ulcerative colitis. Gastroenterol T1187:A-431

46.

Kawamura N, et al (2002) Efficacy of leucocyte apheresis with the use of nonwoven polyester filter in ulcerative colitis. Gastroenterol T1196:A-431

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 Diego

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 154:2434–2440PubMed

49.

Monteleone G, et al (1997) Interleukin 12 is expressed and actively released by Crohn’s disease intestinal lamina propria mononuclear cells. Gastroenterology 112:1169–1178PubMed

50.

Christ AD, et al (1998) An interleukin 12-related cytokine is up-regulated in ulcerative colitis but not in Crohn’s disease. Gastroenterology 115:307–313PubMed

51.

Auphan N, et al (1995) Immunosuppression by glucocorticoids: inhibition of NF-kappa B activity through induction of I kappa B synthesis. Science 270:286–290PubMed

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 119:1209–1218PubMed

53.

Dubuquoy L, et al (2003) Impaired expression of peroxisome proliferator-activated receptor gamma in ulcerative colitis. Gastroenterology 124:1265–1276CrossRefPubMed

54.

Lewis JD, et al (2001) An open-label trial of the PPAR-gamma ligand rosiglitazone for active ulcerative colitis. Am J Gastroenterol 96:3323–3328CrossRefPubMed

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 426:51–60PubMed

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 95:2945–2953PubMed

57.

Elson CO, et al (1995) Experimental models of inflammatory bowel disease. Gastroenterology 109:1344–1367PubMed

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 188

59.

Mombaerts P, et al (1993) Spontaneous development of inflammatory bowel disease in T cell receptor mutant mice. Cell 75:274–282PubMed

60.

Sadlack B, et al (1993) Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell 75:253–261PubMed

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 95:2945–2953PubMed

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 17:629–638PubMed

63.

Mizoguchi E, et al (1997) Antineutrophil cytoplasmic antibodies in T-cell receptor alpha-deficient mice with chronic colitis. Gastroenterology 113:1828–1835PubMed

64.

Lichtiger S, et al (1994) Cyclosporine in severe ulcerative colitis refractory to steroid therapy. N Engl J Med 330:1841–1845CrossRefPubMed

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 187:389–402CrossRefPubMed

66.

Holtmann MH, Galle PR (2003) Therapy-refractory and fulminant, toxic colitis. Dig Surg 20:372–374

67.

Mourelle M, et al (1995) Induction of nitric oxide synthase in colonic smooth muscle from patients with toxic megacolon. Gastroenterology 109:1497PubMed

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:G425

69.

Caprilli R, et al (1987) Early recognition of toxic megacolon. J Clin Gastroenterol 9:136

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 184:682PubMed

71.

Danovitch SH (1989) Fulminant colitis and toxic megacolon. Gastroenterol Clin North Am 18:73PubMed

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 26:158–163PubMed

73.

Langholz E, Munkholm P, Davidson M (1994) Course of ulcerative colitis: analysis of changes in disease activity over years. Gastroenterology 107:3–11PubMed

74.

Bernstein CN, et al (2001) Cancer risk in patients with inflammatory bowel disease. Cancer 48:526–535

75.

Eaden JA, Abrams KR, Mayberry JF (2001) The risk of colorectal cancer in ulcerative colitis. a meta-analysis. Gut 48:526–535CrossRefPubMed

76.

Loftus EV (2003) Does monitoring prevent cancer in inflammatory bowel disease? J Clin Gastroenterol 36[Suppl 1]:S79–S83

77.

Schlemper RJ, et al (2000) The Vienna classification of gastrointestinal epithelial neoplasia. Gut 47:251–255PubMed

78.

Riddell RH, et al (1983) Dysplasia in inflammatory bowel disease. Standardized classification with provisional clinical applications. Hum Pathol 14:931–968PubMed

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 80:366–374PubMed

80.

Bernstein CN, Shanahan F, Weinstein WM (1994) Are we telling patients the truth about surveillance colonoscopy in ulcerative colitis? Lancet 343:71–74PubMed

81.

Provenzale D, Onken J (2001) Surveillance issues in inflammatory bowel disease: ulcerative colitis. J Clin Gastroenterol 32:99–105CrossRefPubMed

82.

Tanaka S, et al (2000) Detailed colonoscopy for detecting early superficial carcinoma; recent developments. J Gastroenterol 35 [Suppl 12]:121–125

83.

Kiesslich R, et al (2003) Methylene blue-aided chromoendoscopy for the detection of intraepithelial neoplasia and colon cancer in ulcerative colitis. Gastroenterology 124:880–888PubMed

Title: Current concept of pathophysiological understanding and natural course of ulcerative colitis
Authors: Martin H. Holtmann
Peter R. Galle
Publication date: 01-10-2004
Publisher: Springer-Verlag
Published in: Langenbeck's Archives of Surgery / Issue 5/2004
Print ISSN: 1435-2443
Electronic ISSN: 1435-2451
DOI: https://doi.org/10.1007/s00423-003-0448-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Current concept of pathophysiological understanding and natural course of ulcerative colitis

Abstract

Introduction

Discussion

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Discussion

Conclusion

Please log in to get access to this content

Other articles of this Issue 5/2004

Steroid administration before partial hepatectomy with temporary inflow occlusion does not influence cyclin D1 and Ki-67 related liver regeneration

Pre-hepatectomy prognostic staging to determine treatment strategy for colorectal cancer metastases to the liver

Prof. Dr med. Dr h.c. Hans Wilhelm Schreiber 1924–2004

8th Annual Meeting on Surgical Research / 8. Chirurgische Forschungstage 2004, 27-30 October 2004, Mannheim, Germany

Long-term pain and recurrence after repair of ventral incisional hernias by open mesh: clinical and MRI study

Ulcerative colitis: conservative management and long-term effects