Skip to main content
SpringerLink
Log in

Effect of treatment with interleukin-1 receptor antagonist on the development of carrageenan-induced pleurisy in the rat

  • Original Articles
  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

Pretreatment of rats with the human interleukin-1 receptor antagonist (IL-1ra) by the subcutaneous route at −0.5 h, relative to the intrapleural injection of carrageenan (CG), suppressed the infiltration of cells into the pleural cavity of intact and adrenalectomized rats at 5 h (28 and 74% reduction in intact animals at 0.3 and 10 mg/kg, respectively). Exudate volume at 5 h was also suppressed at dosages of IL-1ra ≥ 3 mg/kg. IL-1ra was still effective as an antiinflammatory agent in the 5-h pleurisy model when administered 1 or 2 h, but not 3 h, after CG. The addition of IL-1ra to a maximally effective antiinflammatory dosage of indomethacin (5 mg/kg) resulted in further reductions of cell number and exudate volume, suggesting that the antiinflammatory effects of IL-1ra in the 5-h model were not due solely to inhibition of IL-1-induced prostaglandin biosynthesis. The antiinflammatory effects of suboptimal dosages of IL-1ra and dexamethasone, administered in combination, were essentially additive. In 24-h pleurisy, IL-1ra reduced exudate volume and PMN number after a single dosage of 10 mg/kg, subcutaneously at −0.5 h and after dosages of 3 mg/kg at −0.5 and 5 h. Additional dosages of IL-1ra (3 mg/kg) at 10 and 15 h did not further inhibit PMN accumulation. Treatment with IL-1ra did not affect macrophage accumulation in 24-h CG-induced pleurisy. IL-1ra was not active as an antiinflammatory agent in the 24-h pleurisy model after three dosages of IL-1ra (3mg/kg) at 5, 10 and 15 h.

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.

Institutional subscriptions

Similar content being viewed by others

References

  1. Capasso, F., C. J. Dunn, S. Yamamoto, D. A. Willoughby, andJ. P. Giroud. 1975. Further studies of carrageenan-induced pleurisy in rats.J. Pathol. 116:117–124.

    Google Scholar 

  2. Almeida, A. P., B. M. Bayer, Z. Horakova, andM. E. Beaven. 1980. Influence of indomethacin and other antiinflammatory drugs on mobilization and production of neutrophils: Studies with carrageenan-induced inflammation in rats.J. Pharmacol. Exp. Ther. 214:74–79.

    Google Scholar 

  3. Vinegar, R., J. F. Traux, J. L. Selph, andF. A. Voelker. 1982. Pathway of onset, development, and decay of carrageenan pleurisy in the rat.Fed. Proc. 41:2588–2595.

    Google Scholar 

  4. Harada, Y., K. Tanaka, Y. Uchida, A. Ueno, S. Oh-Ishi, K. Yamashita, M. Ishibashi, H. Miyazaki, andM. Katori. 1982. Changes in the levels of prostaglandins and thromboxane and their roles in the accumulation of exudate in rat carrageenan-induced pleurisy—a profile analysis using gas chromatography-mass spectrometry.Prostaglandins 23:881–895.

    Google Scholar 

  5. Kumakura, S., I. Kamo, andS. Tsurufuji. 1988. Role of bradykinin in the vascular permeability response induced by carrageenan in rats.Br. J. Pharmacol. 93:739–746.

    Google Scholar 

  6. Lo, T. N., A. P. Almeida, andM. A. Beaven. 1984. Effect of indomethacin on generation of chemotactic activity in inflammatory exudates induced by carrageenan.Eur. J. Pharmacol. 99:31–43.

    Google Scholar 

  7. Vannier, E., M. Roch-Arveiller, B. Molinie, B. Terlain, andJ. P. Giroud. 1989. Effects of ketoprofen and indomethacin on leukocyte migration in two models of pleurisy induced by carrageenan or zymosan-activated serum in rats.J. Pharmacol. Exp. Ther. 248:286–291.

    Google Scholar 

  8. Sedgwick, A. D., A. R. Moore, A. Al-Duaij, andD. A. Willoughby. 1985. Studies into the association between leukocyte accumulation and oedema formation.Agents Actions 17:209–213.

    Google Scholar 

  9. Utsunomiya, I., S. Nagai, andS. Oh-Ishi. 1991. Sequential appearance of IL-1 and IL-6 activities in rat carrageenin-induced pleurisy.J. Immunol. 147:1803–1809.

    Google Scholar 

  10. Perretti, M., E. Solito, andL. Parente. 1992. Evidence that endogenous interleukin-1 is involved in leukocyte migration in acute experimental inflammation in rats and mice.Agents Actions 35:71–78.

    Google Scholar 

  11. Yoshimura, T., K. Matsushima, S. Tanaka, E. A. Robinson, E. Appella, J. J. Oppenheim, andE. J. Leonard. 1987. Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines.Proc. Natl. Acad. Sci. U.S.A. 84:9233–9237.

    Google Scholar 

  12. Nourshargh, S., J. A. Perkins, H. J. Showell, K. Matsushima, T. J. Williams, andP. D. Collins. 1992. A comparative study of the neutrophil stimulatory activity in vitro and proinflammatory properties in vivo of 72 amino acid and 77 amino acid IL-8.J. Immunol. 148:106–111.

    Google Scholar 

  13. Yoshimura, T., K. Matsushima, J. J. Oppenheim, andE. J. Leonard. 1987. Neutrophil chemotactic factor produced by lipopolysaccharide (LPS)-stimulated human blood mononuclear leukocytes: Partial characterization and separation from interleukin 1 (IL 1).J. Immunol. 139:788–793.

    Google Scholar 

  14. Rampart, M., andT. J. Williams. 1988. Evidence that neutrophil accumulation induced by interleukin-1 requires both local protein biosynthesis and neutrophil CD 18 antigen expression in vivo.Br. J. Pharmacol. 94:1143–1148.

    Google Scholar 

  15. Sayers, T. J., T. A. Wiltrout, C. A. Bull, A. C. Denn, III, A. M. Pilaro, andB. Lokesh. 1988. Effect of cytokines on polymorphonuclear neutrophil infiltration in the mouse: Prostaglandin- and leukotriene-in dependent induction of infiltration by IL-1 and tumor necrosis factor.J. Immunol. 141:1670–1677.

    Google Scholar 

  16. Faccioli, L. H., G. E. P. Souza, F. Q. Cunha, S. Poole, andS. H. Ferreira. 1990. Recombinant interleukin-1 and tumor necrosis factor induce neutrophil migration in vivo by indirect mechanisms.Agents Actions 30:344–349.

    Google Scholar 

  17. Henderson, B., andE. R. Pettipher. 1988. Comparison of the in vivo inflammatory activities after intra-articular injection of natural and recombinant IL-1α and IL-1β in the rabbit.Biochem. Pharmacol. 37:4171–4176.

    Google Scholar 

  18. Osborn, L. 1990. Leukocyte adhesion to endothelium in inflammation.Cell 62:3–6.

    Google Scholar 

  19. Butcher, E. 1991. Leukocyte-endothelial cell recognition: Three (or more) steps to specificity and diversity.Cell 67:1035–1036.

    Google Scholar 

  20. Smith, C. W., T. K. Kishimoto, O. Abbass, B. Hughes, R. Rothlein, L. V. McIntire, E. Butcher, andD. C. Anderson. 1991. Chemotactic factors regulate lectin adhesion molecule 1 (LECAM-1)-dependent neutrophil adhesion to cytokine-stimulated endothelial cells in vitro.J. Clin. Invest. 87:609–618.

    Google Scholar 

  21. Collins, P. D., P. J. Jose, andT. J. Williams. 1991. The sequential generation of neutrophil chemoattractant proteins in acute inflammation in the rabbit in vivo: Relationship between C5a and proteins with the characteristics of IL-8/neutrophil-activating protein 1.J. Immunol. 146:677–684.

    Google Scholar 

  22. Sica, A., K. Matsushima, J. Van Damme, J. M. Wang, N. Polentarutti, E. Dejana, F. Colotta, andA. Mantovani. 1990. IL-1 transcriptionally activates the neutrophil chemotactic factor/IL-8 gene in endothelial cells.Immunology 69:548–553.

    Google Scholar 

  23. Butcher, E. C. 1990. Cellular and molecular mechanisms that direct leukocyte traffic.Am. J. Pathol. 136:3–11.

    Google Scholar 

  24. Arend, W. P. 1991. Interleukin 1 receptor antagonist: A new member of the interleukin 1 family.J. Clin. Invest. 88:1445–1451.

    Google Scholar 

  25. Dinarello, C. A., andR. C. Thompson. 1991. Blocking IL-1: Interleukin 1 receptor antagonist in vivo and in vitro.Immunol. Today 12:404–410.

    Google Scholar 

  26. Mikami, T., andK. Miyasaka. 1983. Effects of several anti-inflammatory drugs on the various parameters involved in the inflammatory response in rat carrageenan-induced pleurisy.Eur. J. Pharmacol. 95:1–12.

    Google Scholar 

  27. Besedovsky, H., A. del Ray, E. Sorkin, andC. A. Dinarello. 1986. Immunoregulatory feedback between interleuldn-1 and glucocorticoid hormones.Science 233:652–654.

    Google Scholar 

  28. Schorlemmer, H. U., D. Bitter-Suermann, andA. C. Allison. 1977. Complement activation by the alternative pathway and macrophage enzyme secretion in the pathogenesis of chronic inflammation.Immunology 32:929–940.

    Google Scholar 

  29. Okusawa, S., C. A. Dinarello, K. B. Yancey, S. Endres, T. J. Lawley, M. M. Frank, J. F. Burke, andJ. A. Gelfand. 1987. C5a induction of human interleukin 1: Synergistic effect with endotoxin or interferon-γ.J. Immunol. 139:2635–2640.

    Google Scholar 

  30. Bevilacqua, M. P., J. S. Pober, D. L. Mendrick, R. S. Cotran, andM. A. Gimbrone. 1987. Identification of an inducible endothelial-leukocyte adhesion molecule.Proc. Natl. Acad. Sci. U.S.A. 84:9238–9242.

    Google Scholar 

  31. Luscinskas, F. W., A. F. Brock, M. A. Arnaout, andM. A. Gimbrone, Jr. 1989. Endothelial-leukocyte adhesion molecule-1-dependent and leukocyte (CD11/CD18) -dependent mechanisms contribute to polymorphonuclear leukocyte adhesion to cytokine-activated human vascular endothelium.J. Immunol. 142:2257–2263.

    Google Scholar 

  32. Goodman, R. B., R. G. Wood, T. R. Martin, O. Hanson-Painton, andG. T. Kinasewitz. 1992. Cytokine-stimulated human mesothelial cells produce chemotactic activity for neutrophils including NAP-1/IL-8.J. Jmmunol. 148:457–465.

    Google Scholar 

  33. Porat, R., D. D. Poutsiaka, L. C. Miller, E. V. Granowitz, andC. A. Dinarello. 1992. Interleukin-1 (IL-1) receptor blockade reduces endotoxin andBorrelia burgdorferi-stimulated IL-8 synthesis in human mononuclear cells.FASEB J. 6:2482–2486.

    Google Scholar 

  34. DeForge, L. E., D. E. Tracy, J. S. Kenney, andD. G. Remick. 1992. Interleukin receptor antagonist protein inhibits interleukin-8 expression in lipopolysaccharide-stimulated human whole blood.Am. J. Pathol. 140:1045–1054.

    Google Scholar 

  35. Meyers, K., andJ. W. Coffey. 1984. Differential effects of cyclooxygenase (CO) and Δ5-lipoxygenase (LO) inhibitors on carrageenan (CG) pleurisy in the rat.Fed. Proc. 43:388.

    Google Scholar 

  36. Bradshaw, D., H. P.Franz, and S. J.Greenham. 1982. Paradoxical effects of indomethacin on 4 hour and 24 hour carrageenan-induced pleurisies.Proc. Br. Pharmacol. Soc. 80:57P.

  37. McIntyre, K. W., G. J. Stephan, K. D. Kolinsky, W. R. Benjamin, J. M. Plocinski, K. L. Kaffka, C. A. Campen, R. A. Chizzonite, andP. L. Kilian. 1991. Inhibition of interleukin-1 binding and bioactivity in vitro and modulation on acute inflammation in vivo by I1-1 receptor antagonist and anti-IL-1 receptor monoclonal antibody.J. Exp. Med. 173:931–939.

    Google Scholar 

  38. Cominelli, F., C. C. Nast, B. D. Clark, R. Schindler, R. Llerena, V. E. Eysselein, R. C. Thompson, andC. A. Dinarello. 1990. Interleukin 1 (IL-1) gene expression, synthesis, and effect of specific IL-1 receptor blockade in rabbit immune complex colitis.J. Clin. Invest. 86:972–980.

    Google Scholar 

  39. Wooley, P. H., J. D. Whalen, D. L. Chapman, A. E. Berger, D. G. Aspar, K. A. Richard, andN. D. Staite. 1990. The effect of an interleukin-1 receptor antagonist protein on type II and antigen-induced arthritis in mice.Arthritis Rheum. 33:S20.

    Google Scholar 

  40. Schwab, J. B., S. K. Anderle, R. R. Brown, F. G. Dalldorf, andR. C. Thompson. 1991. Pro- and anti-inflammatory roles of interleukin-1 in recurrence of bacterial cell wall-induced arthritis in rats.Infect. Immun. 59:4436–4442.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Preclinical Research, Hoffmann-La Roche, Inc., 07110, Nutley, New Jersey

    Kenneth P. Meyers, Cristine L. Czachowski & John W. Coffey

Authors
  1. Kenneth P. Meyers
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Cristine L. Czachowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. John W. Coffey
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meyers, K.P., Czachowski, C.L. & Coffey, J.W. Effect of treatment with interleukin-1 receptor antagonist on the development of carrageenan-induced pleurisy in the rat. Inflammation 17, 121–134 (1993). https://doi.org/10.1007/BF00916099

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00916099

Keywords

Search

Navigation