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Prospective evaluation of interferon-α in treatment of chronic active Crohn's disease

  • Intestinal Disorders, Inflammatory Bowel Disease, Immunology And Microbiology
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Abstract

Several case reports suggested good effects of interferon-α in patients with Crohn's disease. In addition, a decreased production of interferon-α in Crohn's disease has been shownin vitro. Treatment with interferon-α may activate intestinal natural killer cells and down-regulate the overproduction of inflammatory cytokines like interleukin-6 in Crohn's disease. To evaluate the clinical efficacy of interferon-α, we treated 12 patients with a chronic active course of Crohn's disease with recombinant human interferon-α prospectively for 24 weeks. Prednisolone was continuously tapered and discontinued at week 12. The end point of the study was the prevention of worsening of clinical symptoms defined with the Crohn's disease activity index and was monitored by acute-phase proteins, interleukin-6 serum concentrations, and endoscopy. The biochemical activity of interferon-α was measured by 2′,5′-oligo adenylate serum levels. The end point of the study was reached in four patients (33%). In these patients the final Crohn's disease activity index was above 150, which means that they did not achieve clinical remission. All other patients (66%) did not respond to interferon-α and had to be withdrawn prematurely. Interferon-α did not show any beneficial effect on interleukin-6 or acute-phase protein concentrations and on endoscopic activity. The 2′,5′-oligo adenylate levels continuously increased during interferon therapy. Considerable side effects were noted. These results fail to demonstrate a therapeutic role of interferon-α in chronic active Crohn's disease.

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References

  1. Binder V, Hendriksen C, Kreiner S: Prognosis in Crohn's disease—based on results from a regional patient group from the county of Copenhagen. Gut 26:146–150, 1985

    PubMed  Google Scholar 

  2. Klein M, Binder HJ, Mitchell M, Aaronson R, Spiro H: Treatment of Crohn's disease with azathioprine: A controlled evaluation. Gastroenterology 66:916–922, 1974

    PubMed  Google Scholar 

  3. Present DH, Korelitz BI, Wisch N, Glass JL, Sachar DB, Pasternack BS: Treatment of Crohn's disease with 6-mercaptopurine. N Engl J Med 302:981–987, 1980

    PubMed  Google Scholar 

  4. Brynskov J, Freund L, Rasmussen SN, Lauritsen K, Schaffalitzky de Muckadell O, Williams N, Macdonald AS, Tanton R, Molina F, Campanini MC, Bianchi P, Ranzi T, Quarto di Palo F, Malchow-Moller A, Thomsen OO, Tage-Jensen U, Binder V, Riis P: A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease. N Engl J Med 321:845–850, 1989

    PubMed  Google Scholar 

  5. Baron S, Tyring SK, Fleischmann WR, Coppenhaver DH, Niesel DW, Klimpel GR, Stanton J, Hughes TK: The interferons: Mechanisms of action and clinical applications. JAMA 266:1375–1383, 1991

    PubMed  Google Scholar 

  6. Thivolet J, Nicolas JF, Kanitakis J, Lyonnet S, Chouvet: Recombinant interferon α2a is effective in the treatment of discoid and subacute cutaneous lupus erythematodes. Br J Dermatol 122:405–409, 1990

    PubMed  Google Scholar 

  7. Vantrappen G, Coremans G, Billiau A, De Somer P: Treatment of Crohn's disease with interferon: A preliminary clinical trial. Acta Clin Belg 35:238–242, 1980

    PubMed  Google Scholar 

  8. Kamoi S, Suzuki H, Yano Y, Sata M, Matsuo Y, Matsukuma N, Ikeda H, Minami T, Sasaki E, Toyonaga A, Tanikawa K: Immunological studies on the patients with Crohn's disease and a new attempt of interferon treatment. Jpn J Gastroenterol 86:193–199, 1989

    Google Scholar 

  9. Hadziselimovic F, Emmons LR, Schaub U: Interferon-α-2a (Roferon) treatment of inflammatory bowel disease in children and adolescents.In Paediatric Gastroenterology: Inflammatory Bowel Diseases and Morbus Hirschsprung. F. Hadziselimovic, B Herzog (eds). Dordrecht, Kluwer Academic Publishers, 1992, pp 109–123

    Google Scholar 

  10. Capobianchi MR, Fais S, Mercuri F, Boirivant M, Dianzani F, Pallone F: Interferon-alpha (IFN-α) production by human intestinal mononuclear cells. Response to virus in control subjects and in Crohn's disease. Gut 33:897–901, 1992

    PubMed  Google Scholar 

  11. MacDermott R, Bragdon MJ, Kodner IJ, Bertovich MJ: Deficient cell-mediated cytotoxicity and hyporesponsiveness to interferon and mitogenic lectin activation by inflammatory bowel disease peripheral blood and intestinal mononuclear cells. Gastroenterology 90:6–11, 1986

    PubMed  Google Scholar 

  12. Heslop HE, Bianchi ACM, Cordingley FT, Turner M, De Mel WCP, Hoffbrand AV, Brenner MK: Effects of interferon α on autocrine growth factor loops in B lymphoproliferative disorders. J Exp Med 172:1729–1734, 1990

    PubMed  Google Scholar 

  13. Mahida YR, Wu K, Jewell DP: Enhanced production of interleukin 1-beta by mononuclear cells isolated from mucosa with active ulcerative colitis or Crohn's disease. Gut 30:835–838, 1989

    PubMed  Google Scholar 

  14. MacDonald TT, Hutchings P, Choy M-Y, Murch S, Cooke A: Tumor necrosis factor-alpha and interferon-gamma production measured at the single cell level in normal and inflamed human intestine. Clin Exp Immunol 81:301–305, 1990

    PubMed  Google Scholar 

  15. Gross V, Andus T, Caesar I, Roth M, Schölmerich J: Evidence for a continuous stimulation of interleukin-6 production in Crohn's disease but not in ulcerative colitis. Gastroenterology 102:514–519, 1992

    PubMed  Google Scholar 

  16. Malchow H, Ewe K, Brandes JW, Goebell H, Ehms H, Sommer H, Jesdinsky H: European cooperative Crohn's disease study (ECCDS): Results of drug treatment. Gastroenterology 86:249–266, 1984

    PubMed  Google Scholar 

  17. Best WR, Becktel JM, Singleton JW, Kern F Jr.: Development of a Crohn's disease activity index. Gastroenterology 70:439–444, 1976

    PubMed  Google Scholar 

  18. Gasché C, Reinisch W, Gangl A, Lochs H: Serum interleukin-6 concentration in Crohn's disease. Gastroenterology 103:1120–1121, 1992

    PubMed  Google Scholar 

  19. Müller C, Knoflach P, Zielinski CC: T-cell activation in Crohn's disease: Increased levels of soluble interleukin-2 receptor in serum and in supernatants of stimulated peripheral blood mononuclear cells. Gastroenterology 98:639–646, 1990

    PubMed  Google Scholar 

  20. Mary JY, Modigliani R: Development and validation of an endoscopic index of the severity for Crohn's disease: A prospective multicentre study. Gut 30:983–989, 1989

    PubMed  Google Scholar 

  21. Davis GL, Balart LA, Schiff ER, Lindsay K, Bodenheimer HC, Perillo RP, Carey W, Jacobson IM, Payne J, Dienstag JL, Van Thiel DH, Tamburro C, Lefkowitch J, Albrecht J, Carlton Meschievitz C, Ortego TJ, Gibas A, Hepatitis Interventional Therapy Group: Treatment of chronic hepatitis C with recombinant interferon alpha. N Engl J Med 321:1501–1506, 1989

    PubMed  Google Scholar 

  22. Hyams JS, Fitzgerald JE, Treem WR, Wyzga N, Kreutzer DL: Relationship of functional and antigenic interleukin 6 to disease activity in inflammatory bowel disease. Gastroenterology 104:1285–1292, 1993

    PubMed  Google Scholar 

  23. De Wit R, Raasveld MHM, Ten Berge RJM, Van der Wouw PA, Bakker PJM, Veenhof CHN: Interleukin-6 concentrations in the serum of patients with AIDS-associated Kaposi's sarcoma during treatment with interferon-alpha. J Intern Med 229:539–542, 1991

    PubMed  Google Scholar 

  24. Sümer N, Beyler R, Palabiyikoglu M, Erten A, Bahar K, Özden A, Uzunalimoglu Ö: The effect of interferon alpha-2a on clinical and endoscopic findings in chronic active ulcerative colitis.In Inflammatory Bowel Diseases: Pathophysiology as Basis of Treatment. J Schölmerich, W Kruis, H Goebell, W Hohenberger, V Gross (eds). Dordrecht, Kluwer Academic Publisher, 1993, p 524

    Google Scholar 

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Authors and Affiliations

  1. From the Department of Gastroenterology and Hepatology, Department of Clinical Pathology, and Institute of Tumorbiology, University of Vienna, Vienna, Austria

    Christoph Gasché MD, Walter Reinisch MD, Harald Vogelsang MD, Regina Pötzi MD, Va Markis MD, Michael Micksche MD, Hans Peter Wirth MD, Alfred Gangl MD & Herbert Lochs MD

  2. Department of Internal Medicine, Division of Gastroenterology, University of Zürich, Zürich, Switzerland

    Christoph Gasché MD, Walter Reinisch MD, Harald Vogelsang MD, Regina Pötzi MD, Va Markis MD, Michael Micksche MD, Hans Peter Wirth MD, Alfred Gangl MD & Herbert Lochs MD

Authors
  1. Christoph Gasché MD
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  2. Walter Reinisch MD
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  3. Harald Vogelsang MD
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  4. Regina Pötzi MD
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  5. Va Markis MD
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  6. Michael Micksche MD
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  7. Hans Peter Wirth MD
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  8. Alfred Gangl MD
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  9. Herbert Lochs MD
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Gasché, C., Reinisch, W., Vogelsang, H. et al. Prospective evaluation of interferon-α in treatment of chronic active Crohn's disease. Digest Dis Sci 40, 800–804 (1995). https://doi.org/10.1007/BF02064982

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  • DOI: https://doi.org/10.1007/BF02064982

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