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The effect of auranofin and sulphasalazine therapy on circulating levels of interleukin 6 in rheumatoid arthritis patients

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Summary

Serum levels of interleukin 6 (IL-6), primarily a macrophage derived cytokine and soluble interleukin 2 receptor (sIL-2R), a marker of lymphocyte activation are elevated in rheumatoid arthritis (RA). We have found that the second line drugs auranofin (AUR) and sulphasalazine (SASP) do not significantly alter circulating levels of sIL-2R implying that these durgs do not influence lymphocyte activity. The effect of AUR and SASP on IL-6 is not established. In RA patients we have investigated the effect of these second line agents on serum II-6 levels.

Using the B9 bioassay, serum IL-6 was sequentially measured at 0 and 12 weeks in RA patients treated with auranofin (n=26) or sulphasalazine (n=20). Clinical and laboratory indices of disease activity were also assessed. In patients receiving either AUR or SASP, serum IL-6 was significantly reduced. This reduction was parallelled by improvement in clinical indices of disease activity. AUR and SASP significantly reduce serum IL-6 levels in RA patients receiving these treatments. Combining one of these agents with a drug that also influences sIL-2R may be a more rational approach to combining second line therapy in RA.

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References

  1. Pitzalis, C., Kingsley, G., Murphy, J., Panayi, G. Abnormal distribution of the helper-inducer suppressor-inducer T lymphocyte subsets in the rheumatoid joint. Clin Immunol Immunopathol 1987, 45, 252–258.

    Google Scholar 

  2. Schwartz, R.H. A cell culture model for T lymphocyte clonal anergy. Science 1990, 248, 1349–1356.

    Google Scholar 

  3. Rubin, L.A., Nelson, D.L. The soluble interleukin 2 receptor: biology, function and clinical application. Ann Internal Med 1990, 113, 619–627.

    Google Scholar 

  4. Rubin, L.A., Jay, G., Nelson, D.L. The released interleukin 2 receptor binds interleukin 2 efficiently. J Immunol 1986, 137, 3841–3844.

    Google Scholar 

  5. Rubin, L.A., Kurman, C.C., Fritz, M.E., Biddison, W.E., Boutin, B., Yarchoan, R., Nelson, D.L. Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. J Immunol 1985, 135, 3172–3177.

    Google Scholar 

  6. Kingsley, G., Pitzalis, C., Panayi, G.S. Immunogenetic and cellular immune mechanisms in rheumatoid arthritis: relevance to new therapeutic strategies. Br J Rheumatol 1990, 29, 58–64.

    Google Scholar 

  7. Firestein, G.S., Zvaifler, N.J. How important are T cells in chronic rheumatoid synovitis. Arthritis Rheum 1990, 33, 768–773.

    Google Scholar 

  8. Sanz, I., Alboukrek, D. Treatment of rheumatoid arthritis. In: Rheumatoid Arthritis, (Ed.: Fischbach, M.). Churchill Livingstone Inc, London 1991, 99–184.

    Google Scholar 

  9. Porter, D., Madhok, R., Hunter, J.A., Capell, H.A. Prospective trial comparing the use of sulphasalazine and auranofin as second line agents in patients with rheumatoid arthritis. Ann Rheum Dis 1992, 51, 461–464.

    Google Scholar 

  10. Arnett, F.C., Edworthy, S.M., Bloch, D.A. et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988, 31, 315–324.

    Google Scholar 

  11. Aarden, L.A., DeGroot, E.R., Schaap, O.L., Lansdorp, P.M. Production of hybridoma growth factor by human monocytes. Eur J Immunol 1987, 17, 1411–1416.

    Google Scholar 

  12. Mosmann, T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxic assays. J Immunol Meth 1983, 65, 55–63.

    Google Scholar 

  13. Horii, Y., Muraguchi, A., Suematsu, S., Matsuda, T., Yoshizaki, K., Hirano, T., Kishimoto, T. Regulation of BSF-2/IL-6 production by human mononuclear cells. J Immunol 1988, 141, 1529–1535.

    Google Scholar 

  14. Houssiau, F.a., Devogelaer, J.-P., Van Damme, J., Nagant de Deuxchaisnes, C., Van Snick, J. Interleukin 6 in synovial fluid and serum of patients with rheumatoid and other inflammatory arthritides. Arthritis Rheum 1988, 31, 784–787.

    Google Scholar 

  15. Crilly, A., Madhok, R., Watson, J., Capell, H.A. Serum concentrations of soluble interleukin 2 receptor in patients with rheumatoid arthritis: effect of second line drugs. Ann Rheum Disease 1993, 52, 58–60.

    Google Scholar 

  16. Crilly, A., Madhok, R., Watson, J., Capell, H.A., Sturrock, R.D. Production of interleukin 6 by monocytes isolated from RA patients receiving second line drug therapy. Br J Rheumatol 1994, 33, 821–825.

    Google Scholar 

  17. Firestein, G.S., Alvaro-Gracia, J.M., Maki, R. Quantitive analysis of cytokine gene expression in rheumatoid arthritis. J Immunol 1990, 144, 3347–53.

    Google Scholar 

  18. Field, M., Chu, C., Feldmann, M., Maini, R.N. Interleukin 6 localization in the synovial membrane in rheumatoid arthritis. Rheumatol Int 1991, 11, 45–50.

    Google Scholar 

  19. Matsubara, T., Ziff, M. Inhibition of human endothelial cell proliferation by gold compounds. J Clin Invest 1987, 79, 1440–1446.

    Google Scholar 

  20. Matsubara, T., Saura, R., Hirohata, K., Ziff, M. Inhibition of human endothelial cell proliferation in vitro and neovascularization in vivo by D-penicillamine. J Clin Invest 1989, 83, 158–167.

    Google Scholar 

  21. Hirata, S., Matsubara, T., Saura, R., Tateishi, H., Hirohata, K. Inhibition of in vitro vascular endothelial cell proliferation and in vivo neovascularization by low-dose methotrexate. Arthritis Rheum 1989, 32, 1065–1073.

    Google Scholar 

  22. Madhok, R., Wijelath, E., Smith, J., Watson, J., Sturrock, R.D., Capell, H.A. Is the beneficial effect of sulphasalazine due to inhibition of synovial neovascularization? J Rheumatol 1991, 18, 199–202.

    Google Scholar 

  23. Dasgupta, B., Corkill, M., Kirkham, B., Gibson, T., Panayi, G. Serial estimation of interleukin 6 as a measure of systemic disease in rheumatoid arthritis. J Rheumatol 1992, 19, 22–25.

    Google Scholar 

  24. Madhok, R., Crilly, A., Murphy, E., Smith, J., Watson, J., Capell, H.A. Gold therapy lowers interleukin 6 levels in rheumatoid arthritis. J Rheumatol 1993, 20, 630–633.

    Google Scholar 

  25. Barrera, P., Boerbooms, A.M.T., Janssen, E.M. et al. Circulating soluble tumor necrosis factor receptors, interleukin 2 receptors, tumor necrosis factor α and interleukin 6 levels in rheumatoid arthritis: longitudinal evaluation during methotrexate and azathioprine therapy. Arthritis Rheum 1993, 36, 1070–1079.

    Google Scholar 

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Crilly, A., Capell, H.A., Watson, J. et al. The effect of auranofin and sulphasalazine therapy on circulating levels of interleukin 6 in rheumatoid arthritis patients. Clin Rheumatol 14, 561–565 (1995). https://doi.org/10.1007/BF02208155

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