Skip to main content
Log in

Changes in colonic tissue levels of inflammatory mediators in a guinea-pig model of immune colitis

  • Immunosupression and Inflammation
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

An immune colitis based on a delayed-type hypersensitivity reaction was induced in dinitrochlorobenzene (DNCB)-sensitized guinea-pigs by intrarectal challenge with DNCB. A low challenge dose (0.25% DNCB) induced mild inflammatory changes in the distal colon and rectum characterized by goblet cell depletion. A higher challenge concentration (5% DNCB) resulted in severe colonic ulceration with crypt abscess formation. The inflammatory mediators, histamine, 5-hydroxytryptamine (5HT), glandular kallikrein and PGE2 were measured in freeze-dried colonic mucosae. Histamine content was three times control (p<0.01) in 0.25% DNCB induced colitis, although no significant change was observed in 5% DNCB challenged animals. Mucosal 5HT content was significantly reduced (p<0.01) after both challenges. Glandular kallikrein content did not differ from control, while PGE2 was significantly (p<0.05) increased at both challenge doses. The possible significance of these changes with respect to severity of inflammation and aetiology of colitis is discussed.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. R.O. Bicks andE.W. Rosenberg,A chronic delayed hypersensitivity reaction in the guinea-pig colon, Gastroenterology46, 543–549 (1964).

    PubMed  Google Scholar 

  2. P.W. Askenase, W.T. Boone andJ.H. Binder,Colonic basophil hypersensitivity. J. Immunol.120, 198–201 (1978).

    PubMed  Google Scholar 

  3. A.J. Lewis, A.A. Norris andI.J. Zeitlin,Studies on a cell-mediated immune response in the guinea-pig colon, Br. J. Pharmac.66, 499–500P (1979).

    Google Scholar 

  4. A.A. Norris, A.J. Lewis, andI.J. Zeitlin,Actions of anticolitic drugs on a guinea-pig model of immune colitis, Agents and Actions (this issue).

  5. I.J. Zeitlin, Y.N. Singh, F. Lembeck andM. Theiler,The molecular weights of plasma and intestinal kallikreins in rats, Naunyn-Schmiedeberg's Arch. Pharmak.293, 159–161 (1976).

    Article  Google Scholar 

  6. Buffer solutions. InDocumenta Geigy: Scientific Tables, 6th edn pp. 314–315. (Ed.K. Diem) Geigy Pharmaceuticals Publications 1962.

  7. P.A. Shore, A. Bukhalter andV.H. Cohn,A method for the fluorometric assay of histamine in tissues, J. Pharmacol. Exp. Ther.127, 182–186 (1959).

    PubMed  Google Scholar 

  8. A.H. Anton andO.F. Sayre,A modified fluorometric procedure for tissue histamine and its distribution in various animals, J. Pharm. Exp. Ther.166, 285–292 (1969).

    Google Scholar 

  9. R.P. Maickel, R.H. Cox, J. Saillant andF.P. Miller,A method for the determination of serotonin and norepinephrine in discrete areas of rat brain, Int. J. Neuropharmac.7, 275–281 (1968).

    Article  Google Scholar 

  10. G.P. Orczyk andH.R. Behrman,Ovulation blockade by aspirin or indomethacin-in vivo evidence for a role of prostaglandin in gonadotrophin secretion, Prostaglandins1, 3–20 (1972).

    Article  PubMed  Google Scholar 

  11. H.F. Dvorak, B.A. Simpson, R.C. Bast andS. Leskowitz,Cutaneous basophil hypersensitivity III. Participation of the basophil in hypersensitivity to antigen-antibody complexes, delayed hypersensitivity and contact-allergy. Passive transfer, J. Immunol.107, 138–148 (1971).

    PubMed  Google Scholar 

  12. M.A. Goldman, B.A. Simpson andH.F. Dvorak,Histamine and basophils in delayed-type hypersensitivity reactions, J. Immunol.110, 1511–1517 (1973).

    PubMed  Google Scholar 

  13. R.J. Priest, J.W. Rebuck andG.T. Harvey,A new qualitative defect of leucocyte function in ulcerative colitis, Gastroenterology38, 715–720 (1960).

    PubMed  Google Scholar 

  14. L. Juhlin,Basophil leucocytes in ulcerative colitis, Acta Med. Scand.173, 351–359 (1963).

    Google Scholar 

  15. M.A. Verity, S.M. Mellinkoff, M. Frankland andM. Greipel,Serotonin content and argentaffin and paneth cell changes in ulcerative colitis, Gastroenterology43, 24–31 (1962).

    PubMed  Google Scholar 

  16. J.M. Skinner, R. Whitehead andJ. Piris,Argentaffin cells in ulcerative colitis, Gut12, 636–638 (1971).

    Google Scholar 

  17. I.J. Zeitlin andA.N. Smith,Mobilization of tissue kallikretin in inflammatory disease of the colon, Gut14, 133–138 (1973).

    PubMed  Google Scholar 

  18. B.J. Johnson, I.J. Zeitlin, J.F. MacKenzie andR.I. Russell,The kinin system in Crohn's disease and ulcerative colitis, (Abs.) Intl. Cong. Inflammation, Bologna, p. 134 (1978).

  19. S. Fasth, L. Hulten, B.J. Johnson, S. Nordgren andI.J. Zeitlin,Mobilization of colonic kallikrein following pelvic nerve stimulation in the atropinized cat, J. Physiol.285, 471–478 (1978).

    PubMed  Google Scholar 

  20. S.R. Gould, A.R. Brash andM.E. Connolly,Increased prostaglandin production in ulcerative colitis, Lancet2, 98 (1977).

    Article  Google Scholar 

  21. D.W. Harris, P.R. Smith andC.H.J. Swan,Venous prostaglandin-like activity in diarrhoeal states, Gut19, 1057–1058 (1978).

    PubMed  Google Scholar 

  22. P. Sharon, M. Ligumsky, D. Rachmilewitz andV. Zor,Role of prostaglandins in ulcerative colitis. Enhanced production during active disease and inhibition by sulfasalazine, Gastroenterology75, 638–640 (1978).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Norris, A.A., Lewis, A.J. & Zeitlin, I.J. Changes in colonic tissue levels of inflammatory mediators in a guinea-pig model of immune colitis. Agents and Actions 12, 243–246 (1982). https://doi.org/10.1007/BF01965154

Download citation

  • Received:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01965154

Keywords

Navigation