Digestive Diseases and Sciences

, Volume 45, Issue 12, pp 2298–2305 | Cite as

Oral Administration of Avian Tumor Necrosis Factor Antibodies Effectively Treats Experimental Colitis in Rats

  • Katherine L. Worledge
  • Ronald Godiska
  • Terrence A. Barrett
  • John A. Kink


Tumor necrosis factor (TNF) is implicated in the pathogenesis of inflammatory bowel disease. Clinical trials indicate that intravenous infusion of anti-TNF antibody is an effective therapy for Crohn's disease. An oral anti-TNF therapy may be a preferred approach, reducing systemic side effects and eliminating the inconvenience and expense of administering infusions. We tested oral avian anti-TNF antibodies in the acute and chronic phases of a rodent colitis model. Efficacy was compared to sulfasalazine and dexamethsone. Rats with chemically induced colitis were treated orally with anti-TNF antibody, placebo, or comparator. Efficacy was assessed by change in colonic weight, morphology, histology, and tissue myeloperoxidase activity. Oral anti-TNF antibody, in both the acute and chronic phases of the model, significantly decreased all inflammatory end points and proved to be more effective than sulfasalazine and dexamethasone. Oral delivery of avian anti-TNF antibodies is an effective treatment of experimental colitis and may provide advantages to current parenteral anti-TNF antibodies.

Crohn's disease anti-tumor necrosis factor antibody oral antibody therapy 


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  1. 1.
    Hay A, Hay J: Inflammatory bowel disease. Cost of illness. J Clin Gastroenterol 14:309-317, 1992Google Scholar
  2. 2.
    Hanauer SB: Inflammatory bowel disease. N Engl J Med 331:841-848, 1996Google Scholar
  3. 3.
    Papadakis KA, Targan SR: Current theories on the causes of inflammatory bowel disease. Gastroenterol Clin North Am 28:283-296, 1999Google Scholar
  4. 4.
    Zhang M, Tracy KJ: Tumor necrosis factor. In The Cytokine Handbook, 3rd ed. A Thomson (ed). San Diego, Academic Press, 1998, pp 517-548Google Scholar
  5. 5.
    Hawkey CJ: Inflammatory mediators. In Inflammatory Bowel Diseases. RN Allan, JM Rhodes, SB Hanauer (eds). New York, Churchill Livingstone, 1997, pp 521-534Google Scholar
  6. 6.
    Tracy KJ: Tumor necrosis factors. In Cytokines in Health and Disease. DG Remick, JS Friedland (eds). New York, Marcel Dekker, 1997, pp 223-239Google Scholar
  7. 7.
    Targan SR, Hanauer SB, van Deventer SJH, Mayer L, Present DH, Braakman T, DeWoody KL, Schaible TF, Rutgeerts PJ: A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. N Engl J Med 337:1029-1035, 1997Google Scholar
  8. 8.
    Rutgeerts PJ, D'Haens G, Targan S, Vasiliauskas E, Hanauer SB, Present DH, Mayer L, Van Hogezand RA, Braakman T, DeWoody KL, Schaible TF, van Deventer SJ: Efficacy and safety of retreatment with anti-tumor necrosis factor antibody (infliximab) to maintain remission in Crohn's disease. Gastroenterology 117:761-769, 1999Google Scholar
  9. 9.
    Sandborn WJ, Hanauer SB: Antitumor necrosis factor therapy for inflammatory bowel disease: A review of agents, pharmacology, clinical results, and safety. Inflamm Bowel Dis 5:119-133, 1999Google Scholar
  10. 10.
    Nicholls S, Stephens S, Bragger CP, Walker-Smith JA, Mac-Donald TT: Cytokines in stools of children with inflammatory bowel disease or infective diarrhoea. J Clin Pathol 46:757-760, 1993Google Scholar
  11. 11.
    Poulson A, von Wechmar BM, Fazakerley G: Antibodies to proteins from yolk of immunized hens. Immunol Commun 9:495-514, 1980Google Scholar
  12. 12.
    Kink JA, Williams JA: Antibodies to recombinant Clostridium difficile toxins A and B are an effective treatment and prevent relapse of C. difficile-associated disease in a hamster model of infection. Infect Immun 66:2018-2025, 1998Google Scholar
  13. 13.
    Hogan MM, Vogel SN: Production of TNF by rIFN-primed C3H/HeJ (Lpsd) macrophages requires the presence of lipid-A-associated proteins. J Immunol 141:4196-4202, 1988Google Scholar
  14. 14.
    Morris GP, Beck PL, Herridge MS, Depew WT, Szewczuk MR, Wallace JL: Hapten-induced model of chronic inflammation and ulceration in the rat colon. Gastroenterology 96:795-803, 1989Google Scholar
  15. 15.
    Sartor RB: How relevant to human inflammatory bowel disease are current animal models of intestinal inflammation? Aliment Pharmacol Ther 11(suppl 3):89-97, 1997Google Scholar
  16. 16.
    Zingarelli B, Squadrito F, Granziani P, Camerini R, Caputi AP: Effects of zileuton, a new 5-lipoxygenase inhibitor, in experimentally induced colitis in rats. Agents Actions 39:150-156, 1993Google Scholar
  17. 17.
    Elson CO, Beagley KW, Sharmanov AT, Fujihashi K, Kiyono H, Tennyson GS, Cong Y, Black CA, Ridwan BW, McGhee JR: Hapten-induced model of murine inflammatory bowel disease: mucosa immune responses and protection by tolerance. J Immunol 157:2174-2185, 1996Google Scholar
  18. 18.
    Krawisz JE, Sharon P, Stenson WF: Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Gastroenterology 87:1344-1350, 1984Google Scholar
  19. 19.
    Murch SH, Braegger CP, Walker SJ, Mac DT: Location of tumor necrosis factor alpha by immunohistochemistry in chronic inflammatory disease. Gut 34:1705-1709, 1993Google Scholar
  20. 20.
    Elson CO, Sartor RB, Tennyson GS, Riddel RH: Experimental models of inflammatory bowel disease. Gastroenterology 109:1344-1367, 1995Google Scholar
  21. 21.
    Zhang XM, Weber I, Chen MJ: Site-directed mutational analysis of human tumor necrosis factor-areceptor binding site and structure function relationship. J Biol Chem 267:24069-24075, 1992Google Scholar
  22. 22.
    Kuus-Reichel K, Grauer LS, Karavodin LM, Knott C, Krusemeier M, Kay NE: Will immunogenicity limit the use, efficacy, and future development of therapeutic monoclonal antibodies. Clin Diagnostic Lab Immunol 1:365-372, 1994Google Scholar

Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Katherine L. Worledge
    • 1
    • 2
  • Ronald Godiska
    • 1
    • 2
  • Terrence A. Barrett
    • 1
    • 2
  • John A. Kink
    • 1
    • 2
  1. 1.Ophidian Pharmaceuticals, Inc.Madison
  2. 2.Department of Medicine and Microbiology/ImmunologyNorthwestern University Medical SchoolChicago

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