Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1990 Feb;85(2):582–586. doi: 10.1172/JCI114476

Interleukin 1 suppresses inflammation in rabbit colitis. Mediation by endogenous prostaglandins.

F Cominelli 1, C C Nast 1, R Llerena 1, C A Dinarello 1, R D Zipser 1
PMCID: PMC296462  PMID: 2298922

Abstract

Pretreatment with low-dose IL-1 has protective effects in animal models of inflammation or tissue injury, but the mechanisms of these protective effects are not established. To determine if prostaglandins are involved, we administered human recombinant IL-1 beta and measured rectal PGE2 production in rabbits with formalin-immune complex colitis. IL-1 beta (0.3 micrograms/kg) administered 24 h before induction of colitis increased PGE2 (231 +/- 36 to 1,299 +/- 572 pg/ml, P less than 0.01) and reduced subsequent inflammatory cell infiltration index (from 2.8 +/- 0.3 to 1.4 +/- 0.3, P less than 0.02) and edema (from 2.5 +/- 0.3 to 1.3 +/- 0.3, P less than 0.01) compared with vehicle-matched animals. Administration of ibuprofen (10 mg/kg i.v.) together with IL-1 beta prevented the stimulation of PGE2 and the reduction in inflammation. Colonic PGE2 production correlated inversely with subsequent severity of inflammation (P less than 0.02, r = -0.39) and edema (P less than 0.04, r = -0.35). IL-1-administration 30 min before induction of colitis did not affect the severity of inflammation. Similarly, pretreatment with a noninflammatory synthetic peptide (fragment 163-171) of human IL-1 beta, either 30 min or 24 h before colitis induction, did not reduce inflammation or increase prostaglandin synthesis. These data demonstrate that pretreatment with IL-1 beta 24 h before the induction of colitis reduces inflammation by a mechanism that requires prostaglandin synthesis.

Full text

PDF
582

Images in this article

584Image
on p.584

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antoni G., Presentini R., Perin F., Tagliabue A., Ghiara P., Censini S., Volpini G., Villa L., Boraschi D. A short synthetic peptide fragment of human interleukin 1 with immunostimulatory but not inflammatory activity. J Immunol. 1986 Nov 15;137(10):3201–3204. [PubMed] [Google Scholar]
  2. Argenzio R. A., Henrikson C. K., Liacos J. A. Effect of prostaglandin inhibitors on bile salt-induced mucosal damage of porcine colon. Gastroenterology. 1989 Jan;96(1):95–109. doi: 10.1016/S0016-5085(89)80008-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Besedovsky H., del Rey A., Sorkin E., Dinarello C. A. Immunoregulatory feedback between interleukin-1 and glucocorticoid hormones. Science. 1986 Aug 8;233(4764):652–654. doi: 10.1126/science.3014662. [DOI] [PubMed] [Google Scholar]
  4. Boraschi D., Nencioni L., Villa L., Censini S., Bossù P., Ghiara P., Presentini R., Perin F., Frasca D., Doria G. In vivo stimulation and restoration of the immune response by the noninflammatory fragment 163-171 of human interleukin 1 beta. J Exp Med. 1988 Aug 1;168(2):675–686. doi: 10.1084/jem.168.2.675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown J. A., Zipser R. D. Prostaglandin regulation of colonic blood flow in rabbit colitis. Gastroenterology. 1987 Jan;92(1):54–59. doi: 10.1016/0016-5085(87)90839-0. [DOI] [PubMed] [Google Scholar]
  6. Castelli M. P., Black P. L., Schneider M., Pennington R., Abe F., Talmadge J. E. Protective, restorative, and therapeutic properties of recombinant human IL-1 in rodent models. J Immunol. 1988 Jun 1;140(11):3830–3837. [PubMed] [Google Scholar]
  7. Chouaib S., Bertoglio J. H. Prostaglandins E as modulators of the immune response. Lymphokine Res. 1988 Fall;7(3):237–245. [PubMed] [Google Scholar]
  8. Cominelli F., Nast C. C., Dinarello C. A., Gentilini P., Zipser R. D. Regulation of eicosanoid production in rabbit colon by interleukin-1. Gastroenterology. 1989 Dec;97(6):1400–1405. doi: 10.1016/0016-5085(89)90382-x. [DOI] [PubMed] [Google Scholar]
  9. Dinarello C. A. Interleukin-1 and its biologically related cytokines. Adv Immunol. 1989;44:153–205. doi: 10.1016/s0065-2776(08)60642-2. [DOI] [PubMed] [Google Scholar]
  10. Goodwin J. S., Ceuppens J. Regulation of the immune response by prostaglandins. J Clin Immunol. 1983 Oct;3(4):295–315. doi: 10.1007/BF00915791. [DOI] [PubMed] [Google Scholar]
  11. Ham E. A., Soderman D. D., Zanetti M. E., Dougherty H. W., McCauley E., Kuehl F. A., Jr Inhibition by prostaglandins of leukotriene B4 release from activated neutrophils. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4349–4353. doi: 10.1073/pnas.80.14.4349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hodgson H. J., Potter B. J., Skinner J., Jewell D. P. Immune-complex mediated colitis in rabbits. An experimental model. Gut. 1978 Mar;19(3):225–232. doi: 10.1136/gut.19.3.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jacobs C., Young D., Tyler S., Callis G., Gillis S., Conlon P. J. In vivo treatment with IL-1 reduces the severity and duration of antigen-induced arthritis in rats. J Immunol. 1988 Nov 1;141(9):2967–2974. [PubMed] [Google Scholar]
  14. Kao H. W., Zipser R. D. Exaggerated prostaglandin production by colonic smooth muscle in rabbit colitis. Dig Dis Sci. 1988 Jun;33(6):697–704. doi: 10.1007/BF01540433. [DOI] [PubMed] [Google Scholar]
  15. Knudsen P. J., Dinarello C. A., Strom T. B. Prostaglandins posttranscriptionally inhibit monocyte expression of interleukin 1 activity by increasing intracellular cyclic adenosine monophosphate. J Immunol. 1986 Nov 15;137(10):3189–3194. [PubMed] [Google Scholar]
  16. March C. J., Mosley B., Larsen A., Cerretti D. P., Braedt G., Price V., Gillis S., Henney C. S., Kronheim S. R., Grabstein K. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 1985 Jun 20;315(6021):641–647. doi: 10.1038/315641a0. [DOI] [PubMed] [Google Scholar]
  17. Nencioni L., Villa L., Tagliabue A., Antoni G., Presentini R., Perin F., Silvestri S., Boraschi D. In vivo immunostimulating activity of the 163-171 peptide of human IL-1 beta. J Immunol. 1987 Aug 1;139(3):800–804. [PubMed] [Google Scholar]
  18. Neta R., Douches S., Oppenheim J. J. Interleukin 1 is a radioprotector. J Immunol. 1986 Apr 1;136(7):2483–2485. [PubMed] [Google Scholar]
  19. Okusawa S., Gelfand J. A., Ikejima T., Connolly R. J., Dinarello C. A. Interleukin 1 induces a shock-like state in rabbits. Synergism with tumor necrosis factor and the effect of cyclooxygenase inhibition. J Clin Invest. 1988 Apr;81(4):1162–1172. doi: 10.1172/JCI113431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Orencole S. F., Dinarello C. A. Characterization of a subclone (D10S) of the D10.G4.1 helper T-cell line which proliferates to attomolar concentrations of interleukin-1 in the absence of mitogens. Cytokine. 1989 Nov;1(1):14–22. doi: 10.1016/1043-4666(89)91044-2. [DOI] [PubMed] [Google Scholar]
  21. Raz A., Wyche A., Siegel N., Needleman P. Regulation of fibroblast cyclooxygenase synthesis by interleukin-1. J Biol Chem. 1988 Feb 25;263(6):3022–3028. [PubMed] [Google Scholar]
  22. Robert A., Bundy G. L., Field S. O., Nezamis J. E., Davis J. P., Hanchar A. J., Lancaster C., Ruwart M. J. Prevention of cecitis in hamsters by certain prostaglandins. Prostaglandins. 1985 Jun;29(6):961–980. doi: 10.1016/0090-6980(85)90221-7. [DOI] [PubMed] [Google Scholar]
  23. Robertson B., Gahring L., Newton R., Daynes R. In vivo administration of interleukin 1 to normal mice depresses their capacity to elicit contact hypersensitivity responses: prostaglandins are involved in this modification of immune function. J Invest Dermatol. 1987 Apr;88(4):380–387. doi: 10.1111/1523-1747.ep12469071. [DOI] [PubMed] [Google Scholar]
  24. Schumert R., Nast C. C., Cominelli F., Zipser R. D. Effects of 16,16-dimethyl prostaglandin E2 and indomethacin on leukotriene B4 and inflammation in rabbit colitis. Prostaglandins. 1988 Oct;36(4):565–577. doi: 10.1016/0090-6980(88)90050-0. [DOI] [PubMed] [Google Scholar]
  25. Wallace J. L., MacNaughton W. K., Morris G. P., Beck P. L. Inhibition of leukotriene synthesis markedly accelerates healing in a rat model of inflammatory bowel disease. Gastroenterology. 1989 Jan;96(1):29–36. doi: 10.1016/0016-5085(89)90760-9. [DOI] [PubMed] [Google Scholar]
  26. Wallace J. L., Whittle B. J., Boughton-Smith N. K. Prostaglandin protection of rat colonic mucosa from damage induced by ethanol. Dig Dis Sci. 1985 Sep;30(9):866–876. doi: 10.1007/BF01309518. [DOI] [PubMed] [Google Scholar]
  27. Wallach D., Holtmann H., Engelmann H., Nophar Y. Sensitization and desensitization to lethal effects of tumor necrosis factor and IL-1. J Immunol. 1988 May 1;140(9):2994–2999. [PubMed] [Google Scholar]
  28. White C. W., Ghezzi P., Dinarello C. A., Caldwell S. A., McMurtry I. F., Repine J. E. Recombinant tumor necrosis factor/cachectin and interleukin 1 pretreatment decreases lung oxidized glutathione accumulation, lung injury, and mortality in rats exposed to hyperoxia. J Clin Invest. 1987 Jun;79(6):1868–1873. doi: 10.1172/JCI113029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Zipser R. D., Patterson J. B., Kao H. W., Hauser C. J., Locke R. Hypersensitive prostaglandin and thromboxane response to hormones in rabbit colitis. Am J Physiol. 1985 Oct;249(4 Pt 1):G457–G463. doi: 10.1152/ajpgi.1985.249.4.G457. [DOI] [PubMed] [Google Scholar]
  30. van der Meer J. W., Barza M., Wolff S. M., Dinarello C. A. A low dose of recombinant interleukin 1 protects granulocytopenic mice from lethal gram-negative infection. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1620–1623. doi: 10.1073/pnas.85.5.1620. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES