Skip to main content
SpringerLink
Log in

Unique properties of auranofin as a potential anti-rheumatic drug

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

Abstract

Gold salts, auranofin (AF), aurothiomalate (ATM) and aurothioglucose (ATG) displayed immunosuppressive action in a series ofin vitro assays which mimic the cell-cell interactions thought to occur in rheumatoid arthritis. The gold salts inhibited phytohaemagglutinin (PHA)-induced thymidine incorporation and γ-IF production by peripheral blood mononuclear cells, as well as IL-2-induced proliferation of PHA-blasts. The separate addition of IL-2 and γ-IF partly reversed the anti-proliferative effects of ATM and ATG; however, the addition of IL-1 had no effect. ATM and ATG inhibited PHA-stimulated IL-1 production by mononuclear cells but not spontaneous or LPS-induced IL-1 production by adherent monocytes. It was concluded that ATM and ATG inhibited lymphocyte function and lymphocyte-amplification of macrophage function.

The anti-proliferative effects of AF were partly reversed by IL-2 but not by γ-IF or IL-1. AF inhibited PHA-stimulated IL-1 production by mononuclear cells as well as spontaneous and LPS-induced production by adherent cells. It appeared that AF inhibited lymphocyte and macrophage function directly. AF also displayed potential anti-inflammatory activity in that it inhibited PGE2 and collagenase production by proteolytically dispersed rheumatoid synovial cells.

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. J. Karsh, J. H. Klippel, P. H. Plotz, J. L. Decker, D. G. Wright and M. W. Flye,Lymphophoresis in rheumatoid arthritis, Ann. Rheum. Dis.33, 361 (1981).

    Google Scholar 

  2. H. E. Paulus, H. I. Machleder, S. Levine, D. T. Y. Yu and N. S. MacDonald,Lymphocyte involvement in rheumatoid arthritis, Arth. Rheum.20, 1249 (1977).

    Google Scholar 

  3. P. Larsson, R. Holmdahl, L. Dencker and L. Klareskog,In vivo treatment with W3/13 (anti-pan T) but not with OX8 (anti-suppressor/cytotoxic T) monoclonal antibodies impedes the development of adjuvant arthritis in rats. Immunology56, 383 (1985).

    Google Scholar 

  4. J. Sany, J. Clot, M. Ponneau and M. Andory,Antibodies against HLA-DR alleviate symptoms of rheumatoid arthritis, Arth. Rheum.25, 17 (1982).

    Google Scholar 

  5. P. S. Steeg, R. N. Moore, H. M. Johnson and J. J. Oppenheim,Regulation of murine macrophage I a antigen expression by a lymphokine with immune interferon activity, J. Exp. Med.156, 1780 (1982).

    Google Scholar 

  6. R. C. Newton,Effect of interferon on the induction of human monocyte secretion of interleukin-1 activity, Immunology56, 441 (1985).

    Google Scholar 

  7. K. A. Smith, L. B. Lachman, J. J. Oppenheim and M. F. Favata,The functinal relationship of the interleukins, J. Exp. Med.151, 1551 (1980).

    Google Scholar 

  8. Empire Rheumatism Council Sub-Committee,Gold therapy in rheumatoid arthritis: report of a multi-centre controlled trial. Ann. Rheum. Dis.19, 95 (1960).

    Google Scholar 

  9. H. A. Capell, D. S. Cole, K. K. Manghani and R. W. Morris (Eds.),Auranofin, proceedings of a Smith Kline and French International Symposium, Excerpta Medica, Amsterdam 1983.

    Google Scholar 

  10. J. M. Dayer, S. M. Krane, G. G. Russel and D. R. Robinson,Production of collagenase and prostaglandins by isolated adherent rheumatoid synovial cells, Proc. Natl. Acad. Sci. USA73, 945 (1976).

    Google Scholar 

  11. D. Gordon and G. P. Lewis,Effects of piroxicam on mononuclear cells, comparison with other anti-arthritic drugs, Inflammation, Supp. to8, 87 (1984).

    Google Scholar 

  12. O. Martinez-Maza, U. Andersson, J. Andersson, S. Britton and M. DeLey,Spontaneous production of interferon-γ in adult and newborn humans. J. Immunol. 132 (1), 251 (1984).

    Google Scholar 

  13. L. P. Severdeshy, C. V. Benton, W. H. Berger, E. Rinderknecht, R. N. Harkins and M. A. Palladino,Biological and antigenic similarities of murine interferon-γ and macrophage-activating factor, J. Exp. Med.,159, 812 (1984).

    Google Scholar 

  14. C. A. Dinarello,Interleukin-I, Rev. Infect. Dis.6, 51 (1984).

    Google Scholar 

  15. J. J. Hooks, H. M. Moutsopoulos, S. A. Geis, N. I. Stahl, J. L. Decker and A. L. Nokins,Immune interferon in the circulation of patients with autoimmune disease, N. Engl. J. Med.301, 5 (1979).

    Google Scholar 

  16. P. E. Lipsky and M. Ziff,Inhibition of antigen- and mitogen-induced human lymphocyte proliferation by gold compounds, J. Clin. Invest.57, 455 (1977).

    Google Scholar 

  17. A. V. Haq, D. G. Mayernite, C. Orosz and J. J. Rinehart,Interleukin-1 secretion is not required for human macrophage support of T-cell proliferation, Cell. Immunol.87, 517 (1984).

    Google Scholar 

  18. C. E. Brinkerhoff and P. M. Guyre,Increased proliferation of human synovial fibroblasts treated with recombinant immune interferon, J. Immunol.134 (5), 3142 (1985).

    Google Scholar 

  19. L. Klareskog, U. Forsum and D. Kubelitz,Immune function of human synovial cells: phenotypic and T-cell regulatory properties of macrophage-like cells that express HLA-DR, Arthr. Rheum.25, 488 (1982).

    Google Scholar 

  20. D. R. Green, B. Clive, T. A. Ferguson, K. D. Beaman and P. M. Flood,Production of an antigen-specific component of suppressor inducer factor by a helper T-cell clone: possible role of IL-1 at the interface of immunity and tolerance, Br. J. Rheumat.24, (Supp.), 105 (1985).

    Google Scholar 

  21. P. Scheurich, U. Ucer, M. Killian and K. Pfizenmaier, Differential effects of gamma-interferon on human T-cells during primary activationin vitro. In:Cellular and Molecular Biology of Lymphokines, p. 63. Academic Press, New York 1985.

    Google Scholar 

  22. J. G. Hanley and B. Bresnihan,Reduction of peripheral blood lymphocytes in patients receiving gold therapy for rheumatoid arthritis, Ann. Rheum. Dis.44, 299 (1985).

    Google Scholar 

  23. S. B. Mizel, J. M. Dayer, S. M. Krane and S. E. Mergenhagen,Stimulation of rheumatoid synovial cell collagenase and prostaglandin production by partially purified lymphocyte-activating faction (interleukin 1), Proc. Natl. Acad. Sci. USA,78 (4), 2474 (1981).

    Google Scholar 

  24. D. R. Robinson, A. H. Tashjian and L. Levine.Prostaglandin-stimulated bone resorption by rheumatoid synovia, J. Clin. Invest.56, 1181 (1975).

    Google Scholar 

  25. S. M. Krane, S. R. Goldring and J. M. Dayer,Interactions among lymphocytes, monocytes and other synovial cells in the rheumatoid synovium. InLymphokines, 7, p. 75 (Ed. E. Pick). Academic Press, New York 1982.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Royal College of Surgeons, Lincoln's Inn Fields, WC2A 3PN, London

    M. L. Barrett & G. P. Lewis

Authors
  1. M. L. Barrett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. G. P. Lewis
    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

Barrett, M.L., Lewis, G.P. Unique properties of auranofin as a potential anti-rheumatic drug. Agents and Actions 19, 109–115 (1986). https://doi.org/10.1007/BF01977265

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01977265

Keywords

Search

Navigation