Skip to main content
SpringerLink
Log in

Protection by recombinant human interleukin-11 against experimental TNB-induced colitis in rats

  • Intestinal Disorders, Inflammatory Bowel Disease, Immunology, And Microbiology
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The potential effect of recombinant human interleukin-11 (rhIL-11) on trinitrobenzene sulfonic acid (TNB) -induced colitis was investigated in rats. Intrarectal TNB (40 mg in 0.25 ml 40% ethanol) produced significant ulcerative colitis. The lesions were most severe at three days after TNB instillation, and then declined, but lesions were still observed after two weeks. TNB administration also significantly enhanced the colonic mucosal myeloperoxidase (MPO) levels, which paralleled the severity of colitis. The rhIL-11 at subcutaneous doses of 300 or 1000µg/kg daily for seven days, or 1000µg/kg for three days when given after TNB significantly decreased lesion formation in TNB-induced colitis. These treatments also significantly reduced colonic mucosal MPO levels. TNB enhanced colonic mucosal levels of PGE2, LTB4, and TxB2, but these arachidonic acid derivatives were not affected by the present rhIL-11 treatments. TNB administration for three days caused a body weight loss that returned to normal after 14 days. The rhIL-11 significantly reduced colonic lesion severity and reduced colonic fecal blood loss. Given alone, rhIL-11 did not influence body weight. It can be concluded that rhIL-11 was protective against TNB-induced colitis and reactions of colonic MPO, but that these responses were not mediated through modulation of eicosanoid metabolism.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Keshavarzian A, Sedghi S, Kanofsky J, List T, Robinson C, Ibrahim C, Winship D: Excessive production of reactive oxygen metabolites by inflamed colon: Analysis by chemiluminescense probe. Gastroenterology 103:177–185, 1992

    PubMed  Google Scholar 

  2. Kishimoto S, Kobayashi H, Shimizu S, Harumak K, Tamaru T, Kajiyama G, Miyoshi A: Changes of colonic vasocative intestinal peptide and cholinegic activity in rats with chemical colitis. Dig Dis Sci 37:1729–1737, 1992

    PubMed  Google Scholar 

  3. Ekakim R, Karmeli F, Razin E, Rachmilewitz D: Role of platelet-activating factor in ulcerative colitis. Gastroenterol 95:1167–1172, 1988

    PubMed  Google Scholar 

  4. Zeitlin IJ, Smith AN: Mobilization of tissue kallikreins in inflammatory diseases of the colon. Gut 14:133–138, 1973

    PubMed  Google Scholar 

  5. Rampton DS: Colitis and nonsteroidal anti-inflammatory drugs.In Prostaglandins and Leukotrienes in Gastrointestinal Diseases. W Domschke, HG Dammann (eds). Berlin, Springer-Verlag, 1988, pp 254–259

    Google Scholar 

  6. Rachmilewitz D, Simon PL, Schwartz LW, Griswold DE, Fondacano JD, Wasserman MA: Inflammatory mediators of experimental colitis in rats. Gastroenterology 97:326–337, 1989

    PubMed  Google Scholar 

  7. Satsangi J, Wolstencroft R, Cason J, Ainley C, Dumonde D, Thompson R: Interleukin 1 in Crohn's disease. Clin Exp Immunicol 67:594–605, 1987

    Google Scholar 

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

    PubMed  Google Scholar 

  9. Ligumsky M, Simon PL, Karmeli F, Rachmilewitz D: Role of interleukin 1 in inflammatory bowel disease-enhanced production during active disease. Gut 31:686–689, 1990

    PubMed  Google Scholar 

  10. Cominelli F, Nast CC, Duchini A, Lee M: Recombinant interleukin-1 receptor antagonist blocks the proinflammatory activity of endogenous interleukin-1 in rabbit immune colitis. Gastroenterology 103:65–71, 1992

    PubMed  Google Scholar 

  11. Mahida YR, Wu K, Patel S, Jewell DP: Interleukin 2 receptor expression by macrophages in inflammatory bowel disease. Clin Exp Immunol 74:382–386, 1988

    PubMed  Google Scholar 

  12. Brynskov J, Tvede N: Plasma interleukin-2 and a soluble/shed interleukin-2 receptor in serum of patients with Crohn's disease. Gut 31:795–799, 1990

    PubMed  Google Scholar 

  13. Gasche C, Reinisch W, Lochs H, Gangl A: Interleukin-6 production in Crohn's disease. Gastroenterology 103:1120–1121, 1992

    PubMed  Google Scholar 

  14. Gross V, Andus T, Caesar I, Roth M, Scholmerich J: Evidence for continuous stimulation of interleukin 6 production in Crohn's disease. Gastroenterol 102:514–519, 1992

    PubMed  Google Scholar 

  15. MacPherson B, Pfeiffer CJ: Experimental production of diffuse colitis in rats. Digestion 17:135–150, 1978

    PubMed  Google Scholar 

  16. Keith JC Jr, Albert L, Sonis ST, Pfeiffer CJ, Schaub RG: IL-11 A pleiotropic cytokine: Exciting new effects of IL-11 on gastrointestinal mucosal biology. Stem Cells 12(suppl 1):79–90, 1994

    PubMed  Google Scholar 

  17. 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, 1989

    PubMed  Google Scholar 

  18. Pfeiffer CJ, Sato S, Ohsugi R, Hasegawa Y, Fujimori T: Enhancement of dimethylhydrazine-induced preneoplastic pathology in the rat colon by experimental colitis and capsaicin irritation. Digestion 55(suppl):34, 1994 (abstract)

    PubMed  Google Scholar 

  19. Krawisz JE, Sharon P, Stenson WF: Quantitative assay for acute intestinal inflammation based on myeloperoxidase activity. Gastroenterology 87:1344–1350, 1984

    PubMed  Google Scholar 

  20. Schultz J, Kaminker K: Myeloperoxidase of the leukocyte of normal human blood. I. Content and localization. Arch Biochem Biophys 96:465–467, 1962

    PubMed  Google Scholar 

  21. Patriarca P, Cramer R, Marussi M, Rossi F, Romeo D: Mode of activation of granule-bound NADPH oxidase in leukocytes during phagocytosis. Biochim Biophys Acta 237:335–338, 1971

    PubMed  Google Scholar 

  22. Mendeloff AI, Calkins BM: The epidemiology of idiopathic inflammatory bowel disease.In Inflammatory Bowel Disease. JB Kirsner, RG Shorter (eds). Philadelphia, Lea & Febiger, 1988, pp 3–34

    Google Scholar 

  23. Sartor RB: Animal models of intestinal inflammation, relevance to inflammatory bowel disease.In Inflammatory Bowel Disease. RP MacDermott, WF Stenson (eds). New York, Elsevier, 1992, pp 337–353

    Google Scholar 

  24. Boughton-Smith NK, Whittle BJR: Laboratory methods for studying the role of eicosanoids in inflammatory bowel disease.In Eicosanoids and the Gastrointestinal Tract. K Hillier (ed). Boston, MTP Press, 1988, pp 12–45

    Google Scholar 

  25. Yoshida N, Yoshikawa T, Nakamura Y, Arai M, Matsuyama K, Iinuma S, Yagi N, Naito Y, Miyasaka M, Kondo M: Role of neutrophil-mediated inflammation in aspirin-induced gastric mucosal injury. Dig Dis Sci 40:2300–2304, 1995

    PubMed  Google Scholar 

  26. Buell MG, Berin MC: Neutrophil-independence of the initiation of colonic injury, comparison of results from three models of experimental colitis in the rat. Dig Dis Sci 39(12):2575–2588, 1994

    PubMed  Google Scholar 

  27. Musashi M, Yang YC, Paul SR, Clark SC, Sudo T, Ogawa M: Direct and synergistic effects of interleukin 11 on murine hemopoiesis in culture. Proc Natl Acad Sci USA 88(3):765–769, 1991

    PubMed  Google Scholar 

  28. Du XX, Doerschuk CM, Orazi A, Williams DA: A bone marrow stromal-derived growth factor, interleukin-11, stimulates recovery of small intestinal mucosal cells after cytoablative therapy. Blood 83(1):33–37, 1994

    PubMed  Google Scholar 

  29. Yin T, Taga T, Tsang ML, Yasukawa K, Kishimoto T, Yang YC: Involvement of IL-6 signal transducer pg130 in IL-11-mediated signal transduction. J Immunol 151(5):2555–2561, 1993

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. From the Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, 24061, Blacksburg, Virginia

    B. S. Qiu MD, PhD,  C. J. Pfeiffer PhD & J. C. Keith Jr. DVM, PhD

Authors
  1. B. S. Qiu MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. J. Pfeiffer PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. C. Keith Jr. DVM, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Supported by Genetics Institute, Inc., Andover, Massachusetts.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Qiu, B.S., Pfeiffer, C.J. & Keith, J.C. Protection by recombinant human interleukin-11 against experimental TNB-induced colitis in rats. Digest Dis Sci 41, 1625–1630 (1996). https://doi.org/10.1007/BF02087911

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02087911

Key words

Search

Navigation