Role of Leukotrienes in Inflammatory Bowel Disease

  • B. M. Peskar
  • K. M. Müller
  • M. Arndt
  • F. Pelster
Part of the NATO ASI Series book series (NSSA, volume 177)


Ulcerative colitis and Crohn’s disease are characterized by severe mucosal inflammation and mucosal ulceration. As the initiating event of both diseases is not known the aim of drug treatment is to prevent the amplification and/or maintenance of the inflammatory reaction. Development of effective drugs is hampered by the fact that it is not known which chemical mediator/s are responsible for the mucosal inflammation in these patients. Various agents including peptides, vasoactive amines and lipid-derived mediators have been found to elicit the typical reactions found at sites of inflammation such as vasodilation, plasma leakage, activation of inflammatory cells or tissue damage. During an inflammatory event increased formation of several pro-inflammatory agents occurs which may act in concert. Experimental and clinical work is necessary to establish whether inhibition of biosynthesis or action of a certain pro-inflammatory mediator does indeed prevent or reduce symptoms in a given inflammatory disorder.


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  1. 1.
    G. A. Higgs, S. Moncada, and J. R. Vane, Eicosanoids in inflammation, Ann. Clin. Res. 16: 287 (1984).PubMedGoogle Scholar
  2. 2.
    J. R. Vane, Inhibition of prostaglandin synthesis as a mechanism of action for the aspirin-like drugs, Nature 231: 232 (1971).Google Scholar
  3. 3.
    D. S. Rampton and C. J. Hawkey, Prostglandins and ulcerative colitis, Gut 25: 1399 (1984).CrossRefGoogle Scholar
  4. 4.
    K. Lauritsen, L. S. Laursen, K. Bukhave, and J. Rask-Madsen, Effects of topical 5-aminosalicylic acid and prednisolone on prostaglandin E2 and leukotriene B4 levels determined by equilibrium in vivo dialysis of rectum in relapsing ulcerative colitis, Gastroenterology 91: 837 (1986).CrossRefGoogle Scholar
  5. 5.
    T. Gilat, J. Ratan, P. Rosen, and J. Peled, Prostaglandins and ulcerative colitis, Gastroenterology 77: 1083 (1979).Google Scholar
  6. 6.
    D. S. Rampton and G. E. Sladen, Prostaglandin synthesis inhibitors in ulcerative colitis: Flurbiprofen compared with convential treatment, Prostaglandins 21: 417 (1981).CrossRefGoogle Scholar
  7. 7.
    M. A. Bray, Leukotrienes in inflammation, Agents Actions 19: 87 (1986).CrossRefGoogle Scholar
  8. 8.
    P. J. Piper, Formation and actions of leukotrienes, Physiol. Rev. 64: 744 (1984).CrossRefGoogle Scholar
  9. 9.
    P. L. Smith, D. P. Montzka, G. P. McCafferty, M. A. Wassermann, and J. D. Fondacaro, Effect of sulfidopeptide leukotrienes D4 and E4 on ileal ion transport in vitro in the rat and rabbit, Am. J. Physiol. 255: G175 (1988).CrossRefGoogle Scholar
  10. 10.
    P. Sharon and W. F. Stenson, Enhanced synthesis of leukotriene B4 by colonic mucosa in inflammatory bowel disease, Gastroenterology 86: 453 (1984).PubMedGoogle Scholar
  11. 11.
    C. J. Hawkey and A. B. Hawthorne, Medical treatment of ulcerative colitis: scoring the advances, Gut 29: 1298 (1988).CrossRefGoogle Scholar
  12. 12.
    A. Ireland, J. D. Priddle, and D. P. Jewell, Acetylation of 5-aminosalicylic acid by human colonic epithelial cells, Gastroenterology 90: 1471 (1986).Google Scholar
  13. 13.
    M. Campieri, G. A. Lanfranchi, F. Bertoni, C. Brignola, M. R. Minguzzi, and G. Labo, A double-blind clinical trial to compare the effects of 4-aminosalicylic acid to 5-aminosalicylic acid in topical treatment of ulcerative colitis, Digestion 29: 204 (1984).CrossRefGoogle Scholar
  14. 14.
    W. F. Stenson and E. Lobos, Sulfasalazine inhibits the synthesis of chemotactic lipids by neutrophils, J. Clin. Invest. 69: 494 (1982).CrossRefGoogle Scholar
  15. 15.
    N. K. Boughton-Smith, C. J. Hawkey, and B. J. R. Whittle, Biosynthesis of lipoxygenase and cyclo-oxygenase products from (14C)-arachidonic acid by human colonic mucosa, Gut 94: 65 (1983).Google Scholar
  16. 16.
    P. Sharon and W. F. Stenson, Metabolism of arachidonic acid in acetic acid colitis in rats. Similarity to human inflammatory bowel disease, Gastroenterology 88: 55 (1985).CrossRefGoogle Scholar
  17. 17.
    K. W. Dreyling, U. Hoppe, B. A. Peskar, K. Schaarschmidt and B. M. Peskar, Leukotrienes in Crohn’s disease: Effect of sulfasalazine and 5-aminosalicylic acid, Adv. Prostaglandins, Thromboxane and Leukotriene Res 17: 339 (1987).Google Scholar
  18. 18.
    B. M. Peskar, K. W. Dreyling, B. May, K. Schaarschmidt, and H. Goebell, Possible mode of action of 5-aminosalicylic acid, Dig. Dis. Sci. 32: 51S (1987).Google Scholar
  19. 19.
    B. M. Peskar and Ch. Coersmeier, Effect of anti-inflammatory drugs on human colonic leukotriene formation, in: “Inlammatory Bowel Diseases - Basic Research and Clinical Implications” H. Goebell, B. M. Peskar, H. Malchow, eds., pp. 153, MTP Press Ltd., Lancaster, (1988).Google Scholar
  20. 20.
    T. Schlenker and B. M. Peskar, Dual effect of sulphasalazine on colonic prostaglandin synthetase, Lancet 2: 815 (1981).CrossRefGoogle Scholar
  21. 21.
    B. M. Peskar, T. Schlenker, and H. Weiler, Effect of sulphasalazine (SASP) and 5-aminosalicylic acid (5-ASA) on the human colonic prostaglandin system, Gut A444 (1982).Google Scholar
  22. 22.
    H. R. Wittenberg, K. Kleemeyer, U. Hoppe, B. M. Peskar, and B. A. Peskar, Release of eicosanoids from human synovial tissue and the effect of anti-inflammatory drugs, in: “Prostaglandins in Clinical Research” H. Sinzinger and K. Schrör, eds., pp. 277, Alan R. Liss, New York (1987).Google Scholar
  23. 23.
    T. Pullar, J. A. Hunter, and H. A. Capell, Which component of sulphasalazine is active in rheumatoid arthritis? Br. Med. J. 290: 1535 (1985).CrossRefGoogle Scholar
  24. 24.
    K. Lauritsen, J. Hansen, M. Ryde, and J. Rask-Madsen, Colonic azodisalicylate metabolism determined by in vivo dialysis in healthy volunteers and patients with ulcerative colitis, Gastroenterology 86: 1496 (1984).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • B. M. Peskar
    • 1
  • K. M. Müller
    • 2
  • M. Arndt
    • 3
  • F. Pelster
    • 3
  1. 1.Dept. of Experimental Clinical MedicineRuhr-University of BochumGermany
  2. 2.Dept. of Pathology, Bergmannsheil HospitalRuhr-University of BochumGermany
  3. 3.Dept. of SurgeryUniversity of MünsterGermany

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