Skip to main content

Studies ofd-penicillamine on strain variability and lymph node cellularity in adjuvant arthritis

Agents and Actions volume 16, pages 514–520 (1985)Cite this article

Abstract

Experiments were performed in order to ascertain the action ofd-penicillamine (PA) on adjuvant arthritis (AA) in rats and to develop a quantitative evaluation method for PA-like drugs, using Lewis, SD, and Wistar rats. Rats were inoculated in the tail with 0.6 mg ofMycobacterium butyricum suspended in 0.1 ml of liquid paraffin. PA apparently induced enhancement of arthritis only in Lewis rats with a good reproducibility. The enhancing effect of PA was seen when it was administered during the period from day −7 to day −1, from day 0 to day 6, or from day 14 to day 20. In control group of Lewis and Wistar rats, adjuvant caused a rapid increase in the cell number of lymph nodes just after the inoculation, and also a marked increase in spleen cells coinciding with the development of arthritis. In PA-treated Lewis rats, the cell numbers of lymph nodes and spleen significantly surpassed those of control rats. However, PA induced no difference from control in Wistar rats, which were not sensitive to PA treatment during the course of arthritis. These results indicate that AA in Lewis rats is a good model for evaluating the activities of PA-like drugs and that PA may affect lymphocytes in lymph nodes and spleen and induce severer arthritis in Lewis rats.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. R.L. Dawkins, P.J. Zilko, J. Carrano, M.J. Garlepp andB.L. McDonald,Immunobiology of d-penicillamine, J. Rheumatol. (Suppl. 7)8, 51–56 (1981).

    Google Scholar 

  2. S. Otomo, S. Nakaike, I. Tsuji, C. Mori andM. Ohzeki,Studies of d-penicillamine (3): Immunomodulating effect of d-penicillamine, Folia pharmac. jap.77, 313–320 (1981).

    Google Scholar 

  3. H. Fujimura, Y. Hiramatsu, Y. Tamura, M. Yanagihara, A. Kouda, H. Nagai, K. Uda, T. Iso andH. Yamauchi,Pharmacological studies of new sulfhydryl compound 2-mercapto-2-methylpropanoyl-l-cysteine (SA96). Folia pharmac. jap.76, 117–129 (1980).

    Google Scholar 

  4. B. Klamer, E.T. Kimura andM. Makstenieks,Effects of oral cysteine, penicillamine and N-acetylpenicillamine on adjuvant arthritis in rats, Pharmacology1, 283–288 (1968).

    PubMed  Google Scholar 

  5. R. Baumgartner, H. Obenaus andH.C. Staerk,Suppression of adjuvant arthritis by penicillamine in pyridoxine-deficient rats, Proc. Soc. exp. Biol. Med.146, 241–244 (1974).

    PubMed  Google Scholar 

  6. A.J. Anderson,Lysosomal enzyme activity in rats with adjuvant-induced arthritis, Ann. rheum. Dis.29, 307–313 (1970).

    PubMed  Google Scholar 

  7. S.P. Liyanage andH.L.F. Curry,Failure of oral d-penicillamine to modify adjuvant arthritis of immune response in the rat, Ann. rheum. Dis.31, 521 (1972).

    PubMed  Google Scholar 

  8. S. Otomo, S. Higuchi, S. Nakaike, Y. Tarumoto, M. Kimura, M. Sasajima andM. Ohzeki,Studies of D-penicillamine (5): Effects on rat adjuvant arthritis, Folia pharmc. jap.78, 145–162 (1981).

    Google Scholar 

  9. E. Arrigoni-Martelli andE. Bramm,Investigations on the influence of cyclophosphamide, gold sodium thiomalate and d-penicillamine on nystatin oedema and adjuvant arthritis, Agents and Actions5, 264–267 (1975).

    PubMed  Google Scholar 

  10. E. Arrigoni-Martelli, E. Bramm andL. Binderup,Immunostimulant activity of d-penicillamine, Drugs Exp. Clin. Res.2, 189–195 (1977).

    Google Scholar 

  11. M.L. Toivonen, O. Tokola andH. Vapaatalo,Rat adjuvant arthritis as a model to test potential antirheumatic agents, Methods Find. Exp. Clin. Pharmacol.4, 359–363 (1982).

    PubMed  Google Scholar 

  12. A.D. Sedgwick, J.C.W. Edwards andD.A. Willoughby,The effect of d-penicillamine on non-immune responses to tissue injury. Int. J. Tiss. Reac.5, Rehabil.15, 207–210 (1976).

    Google Scholar 

  13. Y. Ohsugi, S.-I. Hata, M. Tanemura, T. Nakano, T. Matsuno, Y. Takagaki, Y. Nishi andM. Shindo,N-(2-Carboxyphenyl)-4-chloroantranilic acid disodium salt: a novel anti-arthritic agent without anti-inflammatory and immunosuppressive activities, J. Pharm. Pharmac.29, 636–637 (1979).

    Google Scholar 

  14. M.W. Whitehouse, I.R. Garrett, B. Vernon-Roberts andP.M. Brooks,Ambivalent effects of anti-arthritic gold drugs on experimental polyarthritis in rats, Int. J. Immunopharmacol.4, 325 (1982).

    Article  Google Scholar 

  15. C.M. Pearson,Experimental joint disease. Observations on adjuvant-induced arthritis, J. Chronic. Dis16, 863–874 (1963).

    Article  PubMed  Google Scholar 

  16. H. Berry, D.A. Willoughby andJ.P. Giroud,Evidence for an endogenous antigen in the adjuvant arthritic rat, J. Path.III, 229–238 (1973).

    Article  Google Scholar 

  17. L. Binderup, E. Bramm andE. Arrigoni-Martelli,Immunological effects of d-penicillamine during experimentally induced inflammation in rats, Scand. J. Immunol.12, 239–247 (1980).

    PubMed  Google Scholar 

  18. E. Bramm, L. Binderup andE. Arrigoni-Martelli,Delayed hypersensitivity to tuberculin in rats: effects of antirheumatic drug, Acta pharamac. tox.44, 75–80 (1979).

    Google Scholar 

  19. E. Arrigoni-Martelli andE. Bramm,Development of models for penicillamine-like drugs, Rheumatol. Rehabil.15, 207–210 (1976).

    PubMed  Google Scholar 

  20. P. Merryman andI.A. Jaffe,Effect of penicillamine on the proliferative response of human lymphocytes, Proc. Soc. exp. Biol. Med.157, 155–158 (1978).

    PubMed  Google Scholar 

  21. K. Kayashima, T. Koga andK. Onoue,Role of T lymphocytes. I. Evidence for the regulatory function of thymus-derived cells in the induction of the disease, J. Immun.117, 1878–1882 (1976).

    PubMed  Google Scholar 

  22. K. Kayashima, T. Koga andK. Onoue,Role of T lymphocytes. II. Different subpopulations of T lymphocytes functioning in the development of the disease, J. Immun.120, 1127–1131 (1978).

    PubMed  Google Scholar 

  23. J.D. Taurog, Studies of the cellular basis of adjuvant arthritis in the rat. InAdvances in Inflammation Research, Vol. 7, pp. 161–170 (Ed. G. Weissmann) Raven Press, New York 1984.

    Google Scholar 

Download references

Author information

Affiliations

  1. Department of Pharmacology, Research Center, Taisho Pharmaceutical Co., Ltd, No. 403, Yoshino-cho 1-chome Ohmiya-shi, 330, Saitama, Japan

    Shiro Nakaike, Kimiyo Takeshita, Mitsue Shiono, Naomi Tomita, Susumo Otomo & Hironaka Aihara

Authors
  1. Shiro Nakaike
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kimiyo Takeshita
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mitsue Shiono
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Naomi Tomita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Susumo Otomo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hironaka Aihara
    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

Nakaike, S., Takeshita, K., Shiono, M. et al. Studies ofd-penicillamine on strain variability and lymph node cellularity in adjuvant arthritis. Agents and Actions 16, 514–520 (1985). https://doi.org/10.1007/BF01983656

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01983656

Keywords

  • Lymph Node
  • Arthritis
  • Paraffin
  • Evaluation Method
  • Quantitative Evaluation