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Current concepts of the pathogenesis of inflammatory bowel disease

Based in part on the annualState of the Art Lecture Irish Society of Gastroenterology, Dublin, November 1993

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Summary

Although the cause of inflammatory bowel disease is not known, the pathogenesis involves an immune-mediated tissue damage that is the result of an interaction among genetic predisposing factors, exogenous triggers and endogenous modifying influences. Multiple genes are involved and operate at the level of the immune response and at the target organ. Exogenous triggers include the enteric microflora which might stimulate the mucosal immune system in genetically predisposed individuals. Endogenous modifying factors such as the psychoneuroendocrine system have regulatory effects on the immune system and the inflammatory response, and may influence the course of the disease. While autoimmune phenomena do occur, particularly in ulcerative colitis, there is no evidence that they are directly responsible for the tissue damage. It appears more likely, particularly in Crohn’s disease, that tissue injury may occur as an indirect or “bystander” effect of mucosal T-cell hyperactivation, perhaps in response to a normal enteric microbial antigen. Most of the immunologic and histologic features of Crohn’s disease can be explained by the effects of T-cell derived and other cytokines on the epithelium, the local immune system, the microvasculature, and the recruitment of auxilliary effector cells such as neutrophils.

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References

  1. Shanahan, F., Targan, S. Mechanisms of tissue injury in inflammatory bowel disease. In: Targan, S., Shanahan, F. (editors). Inflammatory Bowel Disease: From Bench to Bedside. Williams & Wilkins, Baltimore 1994; 78–88.

    Google Scholar 

  2. Shanahan, F. Pathogenesis of ulcerative colitis. Lancet 1993: 342, 407–411.

    Article  PubMed  CAS  Google Scholar 

  3. MacDermott, R. P., Stenson, W. F. Inflammatory bowel disease. In Targan, S., Shanahan, F. eds. Immunology and immunopathology of the liver and gastrointestinal tract. New York/Toronto. Igaku-Shoin: 1990: 459–486.

    Google Scholar 

  4. Shanahan, F. Inflammatory bowel disease, pp 862–866. In: Targan, S. R., moderator. Immunology of intestinal diseases. Ann Intern. Med. 1987: 106, 853–870.

    Google Scholar 

  5. Shanahan, F. The intestinal immune system. In: Physiology of the Gastrointestinal Tract, 3rd edition. Johnson, L. R. (editor), Raven Press, New York 1994: 643–684.

    Google Scholar 

  6. Ferguson, A. Ulcerative colitis and Crohn’s disease. Important and disabling diseases, still underresearched. Br. Med. J. 1994: 309, 355–356.

    CAS  Google Scholar 

  7. Yang, H., Rotter, J. I. The genetics of inflammatory bowel disease. In: Targan, S., Shanahan, F. (eds.) Inflammatory bowel disease: From Bench to Bedside. Williams & Wilkins, Baltimore 1994: 32–64.

    Google Scholar 

  8. Satsangi, J., Jewell, D. P., Rosenberg, W. M. C., Bell, J. I. Genetics of inflammatory bowel disease. Gut 1994: 35, 696–700.

    Article  PubMed  CAS  Google Scholar 

  9. Shanahan, F., Duerr, R. H., Rotter, J. I. Yang, H., Sutherland, L. R., McElree, C., Landers, C. J., Targan, S. R. Neutrophil autoantibodies in ulcerative colitis: familial aggregation and genetic heterogeneity. Gastroenterology 1992: 103, 456–461.

    PubMed  CAS  Google Scholar 

  10. Yang, H., Rotter, J. I., Toyoda, H., Landers, C., Tyan, D., McElree, C. K., Targan, S. R. Ulcerative colitis: a genetically heterogeneous disorder defined by genetic (HLA Class II) and subclinical (antineutrophil cytoplasmic antibodies) markers. J. Clin. Invest. 1993: 92, 1080–1084.

    Article  PubMed  CAS  Google Scholar 

  11. Shanahan, F. Neutrophil autoantibodies in inflammatory bowel disease: are they important? Gastroenterology 1994: 107, 586–589.

    PubMed  CAS  Google Scholar 

  12. Stenson, W. F. Animal models of inflammatory bowel disease. In: Targan, S., Shanahan, F. (editors) Inflammatory bowel disease: From Bench to Bedside. Williams & Wilkins, Baltimore, 1994: 180–192.

    Google Scholar 

  13. Hammer, R. E., Maika, S. D., Richardson, J. A., Tang, J-P., Taurog, J. D. Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human β2m: an animal model of HLA-B27-associated human disorders. Cell 1990: 63, 1099–1112.

    Article  PubMed  CAS  Google Scholar 

  14. Shanahan, F. Gene-targeted immunologic knockouts: new models of inflammatory bowel disease. Gastroenterology 1994: 107, 312–314.

    Google Scholar 

  15. Tysk, C., Riedesel, H., Lindberg, E., Panzini, B., Podolsky, D., Jarnerot, G. Colonic glycoproteins in monozygotic twins with inflammatory bowel disease. Gastroenterology 1991: 100, 419–423.

    PubMed  CAS  Google Scholar 

  16. Helgeland, L., Tysk, C., Jarnerot, G., Kett, K., Lindberg, E., Danielsson, D., Andersen, S. N., Brandtzaeg, P. IgG subclass distribution in serum and rectal mucosa of monozygotic twins with or without inflammatory bowel disease. Gut 1992: 33, 1358–1364.

    Article  PubMed  CAS  Google Scholar 

  17. Rutgeerts, P., Goboes, K., Peeters, M., Hiele, M., Penninckx, F., Aerts, R., Kerremans, R., Vantrappen, G. Effect of faecal stream diversion on recurrence of Crohn’s disease in the neoterminal ileum. Lancet 1991: 338, 771–774.

    Article  PubMed  CAS  Google Scholar 

  18. Madden, M. V., Farthing, M. J. G., Nicholls, R. J. Inflammation in ileal reservoirs: ‘pouchitis’. Gut 1990: 31, 247–249.

    Article  PubMed  CAS  Google Scholar 

  19. Sartor, R. B. Role of intestinal microflora in initiation and perpetuation of inflammatory bowel disease. Can. J. Gastroenterol 1990: 4, 271–277.

    Google Scholar 

  20. James, S. P. Potential role of superantigens in gastrointestinal disease. Gastroenterology 1993: 105, 1569–1571.

    PubMed  CAS  Google Scholar 

  21. Rhodes, J., Thomas, G. A. O. Smoking: good or bad for inflammatory bowel disease? Gastroenterology 1994: 106; 807–810.

    PubMed  CAS  Google Scholar 

  22. Bjarnason, I., Hayllar, J., Macpherson, A. J., Russell, A. S. Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 1993: 104, 1832–1847.

    PubMed  CAS  Google Scholar 

  23. Shanahan, F. The role of autoantibodies and autoimmunity in chronic inflammatory disorders of the gut. Current Opinion in Gastroenterology 1992: 8, 988–992.

    Article  Google Scholar 

  24. Shanahan, F., Targan, S. Mechanisms of tissue injury in inflammatory bowel disease. In: Macdermott, R. P., Stenson, W. F., eds. Current topics in gastroenterology. Inflammatory bowel disease. New York: Elsevier; 1992: 77–93.

    Google Scholar 

  25. MacDonald, T. T., Spencer, J. Evidence that activated mucosal T cells play a role in the pathogenesis of enteropathy in human small intestine. J. Exp. Med. 1988: 167, 1341–1349.

    Article  PubMed  CAS  Google Scholar 

  26. da Cunha Ferreira, R., Forsyth, L. E., Richman, P. I., Wells, C., Spencer, J., MacDonald, T. T. Changes in the rate of crypt epithelial cell proliferation and mucosal morphology induced by a T-cell mediated response in human small intestine. Gastroenterology 1990: 98, 1255–1263.

    PubMed  CAS  Google Scholar 

  27. Vidrich, A., Anton, P., Shanahan, F. Cytokines modulate the growth of normal colonic epithelia. Gastroenterology 1991: 100, A623.

    Google Scholar 

  28. Hermon-Taylor, J., Tizard, M., Sanderson, J. et al. Mycobacteria and the aetiology of Crohn’s disease. In: Rachmilewitz, D., Inflammatory bowel disease 1994, Falk Symposium 72, Kluwer Academic Publishers, The Netherlands, 1993: 51–57.

    Google Scholar 

  29. Wakefield, A. J., Pittilo, R. M., Sim, R., Cosby, S. L., Stephenson, J. R., Dhillon, A. P., Pounder, R. E. Evidence for persistent measles virus infection in Crohn’s disease. J. Medical Virology 1993: 39, 345–353.

    Article  CAS  Google Scholar 

  30. Shanahan, F., Targan, S. Medical treatment of inflammatory bowel disease. Annual Review of Medicine 1992: 43, 125–133.

    PubMed  CAS  Google Scholar 

  31. Mayer, L., Eisenhardt, D. Lack of induction of suppressor T cells by intestinal epithelia cells from patients with inflammatory bowel disease. J. Clin. Invest 1990: 86, 1255–1260.

    Article  PubMed  CAS  Google Scholar 

  32. Sartor, R. B. Cytokines in intestinal inflammation: pathophysiological and clinical considerations. Gastroenterology 1994: 106, 533–539.

    PubMed  CAS  Google Scholar 

  33. Kishimoto, T.K. A dynamic model for neutrophil localization to inflammatory sites. J. NIH Res. 1991: 3, 75–77.

    Google Scholar 

  34. Shanahan, F., Bernstein, C. N. Interleukin 8, neutrophils and acute inflammation. Gastroenterology 1992: 103, 341–343.

    PubMed  CAS  Google Scholar 

  35. Koizumi, M., King, N., Lobb, R., Benjamin, C., Podolsky, D. K. Expression of vascular adhesion molecules in inflammatory bowel disease. Gastroenterology 1992: 103, 840–847.

    PubMed  CAS  Google Scholar 

  36. Parkos, C., Delp, C., Nash, S., Arnaout, A., Madara, J. L. Neutrophil migration across a cultured intestinal epithelium: dependence on a CD 11b/CD18 mediated event and enhanced efficiency in physiological direction. J. Clin. Invest. 1991: 88, 1605–1612.

    Article  PubMed  CAS  Google Scholar 

  37. Weiss, S. J. Tissue destruction by neutrophils. N. Engl. J. Med. 1989: 320, 365–376.

    PubMed  CAS  Google Scholar 

  38. Lobos, E. A., Sharon, P., Stenson, W. F. Chemotactic activity in inflammatory bowel disease. Role of leukotriene B4. Dig. Dis. Sci. 1987: 32, 1380–88.

    Article  CAS  Google Scholar 

  39. Ford-Hutchinson, A. W. Leukotriene B4 inflammation. Critical Reviews in Immunology 1990: 10, 1–12.

    PubMed  CAS  Google Scholar 

  40. Shanahan, F., Anton, P. Neuroendocrine modulation of the immune system. Possible implications for inflammatory bowel disease. Dig. Dis. Sci. 1988: 33, 41S-49S.

    Article  PubMed  CAS  Google Scholar 

  41. Shanahan, F., Anton, P. Role of peptides in the regulation of the mucosal immune and inflammatory response. In: Walsh, J., Dockray, G., eds., Gut peptides: Biochemistry and Physiology. Raven Press Ltd., New York, 1994: 851–867.

    Google Scholar 

  42. Sternberg, E., Chrousos, G. P., Wilder, R. L., Gold, P. W. The stress response and the regulation of inflammatory disease. Ann Intern. Med. 1992: 117, 854–866.

    PubMed  CAS  Google Scholar 

  43. North, C. S., Alpers, D. H., Helzer, J. E., Spitznagel, E. L., Clouse, R. E. Do life stress events or depression exacerbate inflammatory bowel disease? A prospective study. Ann Intern. Med. 1991: 114, 381–386.

    PubMed  CAS  Google Scholar 

  44. Mantyh, C. R., Gates, T. S., Zimmerman, R. P., Welton, M. L., Passaro, E. P., Vigna, S. R., Maggio, R., Kruger, L., Mantyh, P. W. Receptor binding sites for substance P, but not substance K or neuromedin K, are expressed in high concentrations by arterioles, venules, and lymph nodules in surgical specimens obtained from patients with ulcerative colitis and Crohn’s disease. Proc. Natl. Acad. Sci. USA 1988: 85, 3235–3239.

    Article  PubMed  CAS  Google Scholar 

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Shanahan, F. Current concepts of the pathogenesis of inflammatory bowel disease. I.J.M.S. 163, 544–549 (1994). https://doi.org/10.1007/BF02943022

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