Skip to main content
Log in

The efficacy of cyclosporin A, FK-506 and Prednisolone to modify the adoptive transfer of Experimental Allergic Encephalomyelitis (EAE)

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

Abstract

Thein vitro potency of the immunosuppressants Cyclosporin A (CsA), FK-506 and Prednisolone was assessed using the adoptive transfer model of EAE in the Lewis rat. Co-culture of encephalitogen-sensitised splenic leukocytes with Prednisolone did not inhibit the transfer of disease to naive histocompatible recipients despite significant suppression of neuroantigen-stimulated leukocyte proliferation by the drug. The addition of CsA (100 nM) to cultures inhibited the induction of adoptive EAE but a lower dose of the agent (10 nM) did not prevent the development of clinico-histopathological signs of disease. FK-506 (1 nM) was 100 times more effective than CsA at suppressing adoptive EAE thus emphasising the usefulness of the model in determining the relative efficacy of compounds to modify cell-dependent autoimmune disease.

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.

Similar content being viewed by others

References

  1. P. Y. Paterson,Transfer of allergic encephalomyelitis in rats by means of lymph node cells. J. exp. Med.111, 119–135 (1960).

    Article  PubMed  Google Scholar 

  2. A. Ben-Nun, H. Wekerle and I. R. Cohen,The rapid isolation of clonable antigen-specific T lymphocyte lines capable of mediating autoimmune encephalomyelitis. Eur. J. Immunol.11, 195–199 (1981).

    PubMed  Google Scholar 

  3. R. H. Swanborg,Autoimmune effector cells V: a monoclonal antibody specific for rat helper T lymphocytes inhibits adoptive transfer of autoimmune encephalomyelitis. J. Immunol.130, 1503–1505 (1983).

    PubMed  Google Scholar 

  4. A. M. Carbone, H. Ovadia and P. Y. Paterson,Role of macrophage-myelin basic protein interaction in the induction of experimental allergic encephalomyelitis in Lewis rats. J. Immunol.131, 1263–1267 (1983).

    PubMed  Google Scholar 

  5. H. S. Panitch and D. E. McFarlin,Experimental allergic encephalomyelitis: enhancement of cell-mediated transfer by concanavalin A. J. Immunol.119, 1134–1137 (1977).

    PubMed  Google Scholar 

  6. J. R. Richert, B. F. Driscoll, M. Kies and E. C. Alvord,Adoptive transfer of experimentall allergic encepohalomyelitis: Incubation of rat spleen cells with specific antigen. J. Immunol.122, 494–496 (1979).

    PubMed  Google Scholar 

  7. P. Y. Paterson,Autoimmune diseases of myelin. Prog. Clin. Biol. Res.49, 19–36 (1980).

    PubMed  Google Scholar 

  8. B. G. W. Arnason,Relevance of experimental allergic encephalomyelitis to multiple slcerosis. Neurol. Clin.1, 765–782 (1983).

    PubMed  Google Scholar 

  9. C. Bolton, G. Allsopp and M. L. Cuzner,The effect of cyclosporin A on the adoptive transfer of experimental allergic encephalomyelitis in the Lewis rat. Clin. exp. Immunol.47, 127–132 (1982).

    PubMed  Google Scholar 

  10. M. E. Westarp, H. Wekerle, A. Ben-Nun, I. R. Cohen, M. L. Vohl and H. Przuntek,T lymphocyte line-mediated experimental allergic encephalomyelitis — a pharmacologic model for testing of immunosuppressive agents for the treatment of central nervous system disease. J. Pharmacol. Exp. Ther.242, 614–620 (1987).

    PubMed  Google Scholar 

  11. S. Desai and R. Barton,Pharmacological comparison of active and passive experimental allergic encephalomyelitis in the rat. Ag. Act.27, 351–355 (1989).

    Article  Google Scholar 

  12. C. Bolton, J. F. Borel, M. L. Cuzner, A. N. Davison and A. M. Turner,Autoimmunity: Cyclosporin A therapy in Experimental Allergic Encephalomyelitis. InCyclosporin A. (Ed. D. J. G. White) pp. 135–152, Oxford, UK, 1982.

  13. P. Rudge, J. C. Koetsier, J. Mertin, J. O. Mispelblom Beyer, H. K. Van Walbeck, R. Clifford Jones, J. Harrison, K. Robinson, B. Mellein, T. Poole, J. C. J. M. Stokvis and P. Timonen,Randomised double blind controlled trial of cyclosporin in multiple sclerosis. J. Neurol. Neurosurg. Psych.52, 559–565 (1989).

    Google Scholar 

  14. N. Inamura, M. Hashimoto, K. Nakahara, Y. Nakajima, M. Nishio, H. Aoki, I. Yamaguchi and M. Kohsaka,Immunosuppressive effect of FK-506 on experimental allergic encephalomyelitis in rats. Int. J. Immunopharmacol.10, 991–995 (1988).

    Article  PubMed  Google Scholar 

  15. H. Kawashima, Y. Fujino and M. Mochizuki,Effects of a new immunosuppressive agent, FK-506, on experimental autoimmune uveoretinitis in rats. Invest. Opthalmol. Vis. Sci.29, 1265–1271 (1988).

    Google Scholar 

  16. N. Inamura, M. Hashimoto, K. Nakahara, H. Aoki, I. Yamaguchi and M. Kohsaka,Immunosuppressive effect of FK-506 on collagen-induced arthritis in rats. Clin. Immunol. Immunopathol.46, 82–90 (1988).

    Article  PubMed  Google Scholar 

  17. K. Takagishi, M. Yamamoto, A. Nishimura, G. Yamasaki, N. Kanazawa, T. Hotokebuchi and Kaibara,Effect of FK-506 on collagen arthritis in mice. Transplant Proc.21, 1056–1058 (1989).

    PubMed  Google Scholar 

  18. K. Takabayashi, T. Koike, K. Kurasawa, R. Matsumura, T. Sato, H. Tomioka, I. Ito, T. Yoshiki and S. Yoshida,Effect of FK-506, a novel immunosuppressive drug on murine systemic lupus erythematosus. Clin. Immunol. Immunopathol.46, 82–90 (1989).

    Google Scholar 

  19. P. R. Dunkley and P. Carnegi,Isolation of myelin basic proteins. InResearch Methods in Neurochemistry Vol. 2, (Eds. N. M. and R. Rodnight) pp. 219–245, Plenum Press, N.Y. 1974.

    Google Scholar 

  20. S. Levine and R. Sowinski,Suppression of the hyperacute form of experimental allergic encephalomyelitis by drugs. Arch. Int. Pharmacodyn.230, 309–318 (1977).

    PubMed  Google Scholar 

  21. S. L. Abreu,Interferon in experimental autoimmune encephalomyelitis (EAE): Effects of interferon on the antigen-enhanced adoptive transfer of EAE. Int. Archs. Allergy Appl. Immun.76, 302–307 (1985).

    Google Scholar 

  22. S. Sawada, G. Suzuki, Y. Kawase and F. Takaku,Novel immunosuppressive agent, FK-506. In vitro effects on the cloned T-cell activation. J. Immunol.139, 1797–1803 (1987).

    PubMed  Google Scholar 

  23. J. Woo, M. Stephen and A. W. Thompson,Spleen lymphocyte populations and expression of activation markers in rats treated with the potent new immunosuppressive agent FK-506. Immunology65, 153–155 (1988).

    PubMed  Google Scholar 

  24. J. E. Kay, S. E. Doe and C. R. Benzie,The mechanism of action of the immunosupressive drug FK-506. Cell. Immunol.124, 175–181 (1989).

    Article  PubMed  Google Scholar 

  25. T. Kino, H. Hatanaka, S. Miyata, N. Inamura, M. Nishiyama, T. Yajima, T. Goto, M. Okuhara, M. Kohsaka, H. Aoki and T. Ochiai,FK-506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK-506 in vitro. J. Antibiot. (Tokyo)40, 1256–1265 (1987).

    Google Scholar 

  26. M. J. Tocci, D. A. Matkovich, K. A. Collier, P. Kwot, F. Dumont, S. Lin, S. Degudicibus, J. J. Siekierka, J. Chin and N. I. Hutchinson,The immunosuppressant FK-506 selectively inhibits expression of early T cell activation genes. J. Immunol.143, 718–726 (1989).

    PubMed  Google Scholar 

  27. F. J. Dumont, M. J. Stanch, S. L. Koprak, M. R. Melinon and N. H. Sigal,Distinct mechanisms of suppression of murine T cell activation by the related macrolides FK-506 and rapamycin. J. Immunol.144, 2151–258 (1990).

    Google Scholar 

  28. H. G. A. Bouwer, G. N. Dietsch and D. J. Hinrichs,Adoptive transfer of experimental allergic encephalomyelitis: conditions influencing memory and effector cell development. Cell Immunol.131, 219–231 (1990).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bolton, C. The efficacy of cyclosporin A, FK-506 and Prednisolone to modify the adoptive transfer of Experimental Allergic Encephalomyelitis (EAE). Agents and Actions 35, 79–84 (1992). https://doi.org/10.1007/BF01990955

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01990955

Keywords

Navigation