Skip to main content
Log in

Comparative study of effects of cyclosporins A and G on collagen arthritis in mice

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

Abstract

The effects of the immunosuppressive agents cyclosporin G (CsG) and cyclosporin A (CsA) on collagen arthritis were compared in mice. When administered subcutaneously daily on days 0–13 after immunization with type II collagen, CsG and CsA were both capable of suppressing the development of collagen arthritis in mice as well as the immunological response to native type II collagen in a dose-dependent manner. Histopathologically, no marked inflammatory lesions were observed in diarthroidal joints from mice treated with 100 mg/kg per day of CsA or 800 mg/kg per day of CsG. However, an analysis of dose response showed CsG to be 8 times less potent than CsA in inhibiting the development of arthritis.

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. D. E. Trentham, A. S. Townes and A. H. Kang,Autoimmunity to type II collagen: An experimental model of arthritis. J. Exp. Med.146, 857–868 (1977).

    PubMed  Google Scholar 

  2. J. S. Courtenay, M. J. Dallman, A. D. Dayan, A. Martin and B. Mosedale,Immunization against heterologous type II collagen induces arthritis in mice. Nature283, 666–668 (1980).

    PubMed  Google Scholar 

  3. E. S. Cathcart, K. C. Hayes, W. A. Gonnerman, A. A. Lazzari and C. Franzbrau,Experimental arthritis in a nonhuman primate. I. Induction by bovine type II collagen. Lab. Invest.54, 26–31 (1986).

    PubMed  Google Scholar 

  4. D. E. Trentham,Collagen arthritis as a relevant model for rheumatoid arthritis: Evidence pro and con. Arth. Rheum.25, 911–916 (1982).

    Google Scholar 

  5. J. M. Stuart, M. A. Cremer, A. S. Townes and A. H. Kang,Type II collagen-induced arthritis in rats: Passive transfer with serum and evidence that IgG anticollagen antibodies can cause arthritis. J. Exp. Med.155, 1–16 (1982).

    PubMed  Google Scholar 

  6. J. M. Stuart and F. J. Dixon,Serum transfer of collagen-induced arthritis in mice. J. Exp. Med.158, 378–392 (1983).

    PubMed  Google Scholar 

  7. N. Kaibara, M. Morinaga, C. Arita, T. Hotokebuchi and K. Takagishi,Serum transfer of collagen arthritis in cyclosporin-treated, type II collagen-tolerant rats. Clin. Immunol. Immunopathol.35, 252–260 (1985).

    PubMed  Google Scholar 

  8. K. Takagishi, N. Kaibara, T. Hotokebuchi, C. Arita, M. Morinaga and K. Arai,Serum transfer of collagen arthritis in congenitally athymic nude rats. J. Immunol.134, 3864–3867 (1985).

    PubMed  Google Scholar 

  9. M. Dougados, H. Awada and B. Amor,Cyclosporine in rheumatoid arthritis: A double blind placebo controlled study in 52 patients. Ann. Rheum. Dis.47, 127–133 (1988).

    PubMed  Google Scholar 

  10. M. E. Weinblatt, J. S. Coblyn, P. A. Fraser, R. J. Anderson, J. Spragg, D. E. Trentham and K. R. Austen,Cyclosporin A treatment of refractory rheumatoid arthritis. Arth. Rheum.30, 11–17 (1987).

    Google Scholar 

  11. A. W. A. M. van Rijthoven, B. A. C. Dijkmans, The H. S. Goei, M. Boers and A. Cats,Longterm cyclosporine therapy in rheumatoid arthritis. J. Rheumatol.18, 19–23 (1991).

    PubMed  Google Scholar 

  12. P. C. Hiestand, H. Gunn, J. Gale, H. Seigl, B. Ryffel, P. Donatsch and J. F. Borel,The immunosuppressive profile of a new natural cyclosporin analogue: Nva 2-C-cyclosporin. Transplant. Proc.17, 1362–1364 (1985).

    Google Scholar 

  13. P. C. Hiestand, H. C. Gunn, J. M. Gale, B. Ryffell and J. F. Borel,Comparison of the pharmacological profiles of cyclosporine, (Nva 2)-cyclosporin and (Val 2)dihydrocyclosporin. Immunology55, 249–255 (1985).

    PubMed  Google Scholar 

  14. N. Kaibara, T. Hotokebuchi, K. Takagishi and I. Katsuki,Paradoxical effects of cyclosporin A on collagen arthritis in rats. J. Exp. Med.158, 2007–2015 (1983).

    PubMed  Google Scholar 

  15. F. D. Wood, C. M. Pearson and A. Tanaka,Capacity of myocabacterial Wax D and its subfractions to induce adjuvant arthritis in rats. Int. Arch. Allergy Appl. Immunol.35, 456–467 (1969).

    PubMed  Google Scholar 

  16. N. Kaibara, T. Hotokebuchi, K. Takagishi, I. Katsuki, C. Morinaga, C. Arita and S. Jingushi,Pathogenetic difference between collagen arthritis and adjuvant arthritis. J. Exp. Med.159, 1388–1396 (1984).

    PubMed  Google Scholar 

  17. K. Takagishi, N. Kaibara, T. Hotokebuchi, C. Arita, M. Morinaga and K. Arai,Effects of cyclosporin on collagen induced arthritis in mice. Ann. Rheum. Dis.45, 339–344 (1986).

    PubMed  Google Scholar 

  18. M. A. Cremer, A. D. Hernandez, A. S. Townes, J. M. Stuart and A. H. Kang,Collagen-induced arthritis in rats: Antigenspecific suppression of arthritis and immunity by intravenously injected native type II collagen. J. Immunol.131, 2995–3000 (1983).

    PubMed  Google Scholar 

  19. K. Takagishi, M. Yamamoto, A. Nishimura, G. Yamasaki, N. Kanazawa, T. Hotokebuchi and N. Kaibara,Effects of Fk-506 on collagen arthritis in mice. Tansplant. Proc.21, 1053–1055 (1989).

    Google Scholar 

  20. B. Ryffel,Pharmacology of cyclosporine VI. Cellular activation: Regulation of intercellular events by cyclosporine. Pharmacol. Rev.41, 407–422 (1989).

    Google Scholar 

  21. E. G. Hoyt, R. C. Hagberg, M. E. Billinggham, J. C. Baldwin and S. W. Jamieson,Analysis of the immunosuppressive and nephrotoxic effects of cyclosporin G. J. Heart Transpl.7, 111–117 (1988).

    Google Scholar 

  22. D. Grant, R. Zhong, C. Stiller, C. Wallace, P. Keown and J. Duff,A comparison of cyclosporine A and Nva 2-cyclosporine (cyclosporine G) in a rat renal allograft model. Transplantation44, 9–12 (1988).

    Google Scholar 

  23. R. B. Nussenblatt, R. R. Caspi, W. J. U. Dinning, A. G. Palestine, P. Hiestand and J. Borel,A comparison of effectiveness of cyclosporine A, D and G in the treatment of experimental autoimmune uveitis in rats. J. Immunopharmacology8, 427–435 (1986).

    Google Scholar 

  24. R. Y. Calne, D. J. D. White, S. Thiru, K. Rolles, S. Drakopoulos and N. V. Jamieson,Cyclosporin G: Immunosupressive effect in dogs with renal allografts. Lancet1, 1342 (1985).

    Google Scholar 

  25. H. Kawashima, M. Mochizuki, K. Okumura, Y. Fujino, T. Tange, D. Horiuchi, E. Higashihara, H. Kaku and G. Inaba,Cyclosporine G and D in experimental autoimmune uveoretinitis in the rat. Jap. J. Ophthalmol.33, 425–440 (1989).

    Google Scholar 

  26. J. R. Jeffery,Cyclosporine analogues. Clin. Biochem.24, 15–21 (1991).

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Takagishi, K., Yamamoto, M., Miyahara, H. et al. Comparative study of effects of cyclosporins A and G on collagen arthritis in mice. Agents and Actions 37, 284–289 (1992). https://doi.org/10.1007/BF02028121

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02028121

Keywords

Navigation