Clinical Rheumatology

, Volume 14, Issue 4, pp 458–463 | Cite as

Serum soluble interleukin-2 receptor levels in rheumatoid arthritis: Effect of methotrexate, sulphasalazine a d hydroxychloroquine therapy

  • F. Salaffi
  • M. Carotti
  • C. Cervini
Originals

Summary

The aim of this study was to assess the correlations of the serum soluble interleukin 2 receptor (sIL-2R) concentrations with disease activity parameters and response to treatment with second line drugs in patients with rheumatoid arthritis (RA). Sixty-seven patients with active disease completed a 24-week, open, randomized study of methotrexate (MTX) versus sulphasalazine (SSZ) or hydroxychloroquine (HCQ). Serum sIL-2R levels were evaluated before entry and after 24 weeks by ELISA. Serum sIL-2R were significantly higher in RA patients than in controls (P=0.0001) and correlated significantly only with erythrocyte sedimentation rate (P=0.03) and with Chronic Arthritis Systemic Index (P=0.01) at study entry. No correlation was found between serum sIL-2R and other laboratory and clinical indices of disease activity. After 24 weeks of treatment no differences in serum sIL-2R in comparison with basal levels were found in either responding or in non-responding patients, although the mean reduction of sIL-2R was more marked in the MTX-treated cohort than in the HCQ and SSZ-treated groups. These data suggest that in RA the measurement of sIL-2R should be used with caution as an isolated index of disease activity and that it is not a useful marker of response to treatment with second line drugs.

Key words

Serum sIL-2R Rheumatoid Arthritis Methotrexate Sulphasalazine Hydroxychloroquine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Rubin, L.A., Kurman, C.C., Fritz, M.E., et al. Soluble interleukin-2 receptors are released from activated human lymphoid cells in vitro. J Immunol 1985, 135, 3172–3177.PubMedGoogle Scholar
  2. 2.
    Rubin, L.A., Kurman, C.C., Biddison, W.E., Goldman, N.D., Nelson, D.L. A monoclonal antibody, 7G7/B6, binds to an epitope on the human interleukin-2 (IL-2) receptor that is distinct from that recognized by IL-2 or anti-Tac. Hybridoma 1985, 4, 91–102.PubMedGoogle Scholar
  3. 3.
    Semenzato, G., Pizzolo, G., Zambello, R. The interleukin-2/interleukin-2 receptor system: structural, immunological and clinical features. Int J Clin Lab Res 1992, 22, 133–142.PubMedGoogle Scholar
  4. 4.
    Waldmann, A.T. The IL/IL2 receptor system: a target for rational immune intervention. Immunol Today 1993, 14, 264–270.PubMedGoogle Scholar
  5. 5.
    Takeshita, T., Asao, H., Ohtani, K., et al. Cloning of the gamma chain of the human IL-2 receptor. Science 1992, 257, 379–382.PubMedGoogle Scholar
  6. 6.
    Robb, R.J., Kutny, R.M. Structure-function relationships for the IL-2 receptor system. IV. Analysis of the sequence and ligand binding properties at the soluble Tac protein. J Immunol 1987, 139, 855–862.PubMedGoogle Scholar
  7. 7.
    Rubin, L.A. The soluble interleukin-2 receptor in rheumatic diseases. Arthritis Rheum 1990, 33, 1137–45.PubMedGoogle Scholar
  8. 8.
    Rubin, L.A., Snow, K.M., Kurman, C.C., Nelson, D.L., Keystone, E.C. Serial levels of soluble interleukin 2 receptor in the peripheral blood of patients with rheumatoid arthritis: correlation with disease activity. J Rheumatol 1990, 17, 597–602.PubMedGoogle Scholar
  9. 9.
    Keystone, E.C., Snow, K.M., Bombardier, C., Chang, C.H., Nelson, D.L., Rubin, L.A. Elevated soluble interleukin-2 receptor levels in the sera and synovial fluids of patients with rheumatoid arthritis. Arthritis Rheum 1988, 31, 844–849.PubMedGoogle Scholar
  10. 10.
    Campen, D.H., Horwitz, D.A., Quismorio, P., Jr., Ehresmann, G.R., Martin, W.J. Serum levels of interleukin-2 receptor and activity of rheumatic diseases characterized by immune system activation. Arthritis Rheum 1988, 31, 1358–1364.PubMedGoogle Scholar
  11. 11.
    Wolf, R., Brelsford, W.G. Soluble interleukin-2 receptors in systemic lupus erythematosus. Arthritis Rheum 1988, 31, 729–735.PubMedGoogle Scholar
  12. 12.
    Wagner, P.K., Kiwanuka, J., Magrath, I.T., Edwards, B.K., Rubin, L.A., Nelson, D.L. Soluble interleukin-2 receptor levels in undifferentiated and lymphoblastic lymphoma patients. J Clin Oncol 1987, 8, 1262–1274.Google Scholar
  13. 13.
    Polisson, R.P., Dooley, M.A., Awson, D.V., Pisetsky, D.S. Interleukin-2 receptor levels in the sera of rheumatoid arthritis patients treated with methotrexate. Arthritis Rheum 1994, 1, 50–56.Google Scholar
  14. 14.
    Carotti, M., Salaffi, F., Ferraccioli, G.F., Binci, M.C., Sartini, A., Cervini, C. Soluble interleukin-2 receptor in sera and synovial fluids of rheumatoid patients: correlations with disease activity. Rheumatol Int 1994, 14, 47–52.PubMedGoogle Scholar
  15. 15.
    Barrera, P., Boerbooms, A.M.T., Janssen, E.M., et al.: Circulating soluble tumor necrosis factor receptors, interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-6 levels in rheumatoid arthritis. Longitudinal evaluation during methotrexate and azathioprine therapy. Arthritis Rheum 1993, 36, 1070–1079.PubMedGoogle Scholar
  16. 16.
    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.PubMedGoogle Scholar
  17. 17.
    Host, H.J., Flad, H.D. Corticosteroid-interleukin 2 interactions: inhibition of binding of interleukin 2 to interleukin 2 receptors. Clin Exp Immunol 1987, 68, 156–161.PubMedGoogle Scholar
  18. 18.
    Boumpas, D.T., Paliogianni, F., Anastassiou, E.D., Balow, J.E. Glucocorticosteroid action on the immune system: molecular and cellular aspects. Clin Exp Rheumatol 1991, 9, 413–423.PubMedGoogle Scholar
  19. 19.
    Van den Brink, H.R., Van Wijk, M.J.G., Geertzen, R.G.M., Bijlsma, J.W.J. Influence of corticosteroid pulse therapy on the serum levels of soluble interleukin 2 receptor, interleukin 6 and interleukin 8 in patients with rheumatoid arthritis. J Rheumatol 1994, 21, 430–434.PubMedGoogle Scholar
  20. 20.
    Ritchie, D.M., Boyle, J.A., McInnes, J.M., Grieveson, P., Buchanan, W. Clinical studies with an articular index for the assessment of joint tenderness in patients with rheumatoid arthritis. Q J Med 1968, 37, 393–406.PubMedGoogle Scholar
  21. 21.
    Fries J.F., Spits, P., Kraines, R.G., Holman, H.R. Measurement of patients outcome in arthritis. Arthritis Rheum 1980, 23, 137–145.PubMedGoogle Scholar
  22. 22.
    Salaffi, F., Carlino, G., De Angelis, R., Peroni, M., Cervini, C. Chiromorphoergometry: a method for the evaluation and monitoring of functional impairment in rheumatoid hand.Rev Esp Reumatol 1994, 21, 268–273.Google Scholar
  23. 23.
    Ferraccioli, G.F., Salaffi, F., Troise-Rioda W., Bartoli, E. The Chronic Arthritis Systemic Index. Clin Exp Rheumatol 1994, 12, 241–247.PubMedGoogle Scholar
  24. 24.
    Symons, J.A., Wood, N.C., Di Giovine, F.S., Duff, G.W. Soluble IL-2 receptor in rheumatoid arthritis. Correlation with disease activity, IL-1 and IL-2 inhibition. J. Immunol. 1988, 141, 2612–1618.PubMedGoogle Scholar
  25. 25.
    Wood, N.C., Symons, J.A., Dutz, G.W. Serum interleukin-2 receptor in rheumatoid arthritis: a prognostic indicator of disease activity? J Autoimmunity 1988, 1, 353–361.Google Scholar
  26. 26.
    Matsumoto, T., Iwasaki, K. Clinical and laboratory parameters which affect soluble interleukin-2 receptor levels in the serum and synovial fluids with rheumatoid arthritis. Ann Rheum Dis 1993, 52, 876–880.PubMedGoogle Scholar
  27. 27.
    Zielinski, C.C., Resau, B., Muller, C.H. Soluble interleukin-2 receptor and soluble CD8 antigen in active rheumatoid arthritis. Clin Immunol Immunopathol 1990, 57, 74–82.PubMedGoogle Scholar
  28. 28.
    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 Dis 1993, 52, 58–60.PubMedGoogle Scholar
  29. 29.
    Boiardi, L., Macchioni, P., Salvarani, C. et al.: Serum soluble interleukin-2 receptor levels in rheumatoid arthritis: correlation with clinical and immunological parametes and with the response to auranofin treatment. Clin Exp Rheumatol 1994, 12, 357–362.PubMedGoogle Scholar
  30. 30.
    Harrington, L., Affleck, G., Urrows, S. et al. Temporal covariation of soluble interleukin-2 receptor levels, daily stress, disease activity in rheumatoid arthritis. Arthritis Rheum 1993, 36, 199–203.PubMedGoogle Scholar
  31. 31.
    Corkill, M.M., Kirkham, B.W., Dasgupta, B., Gibson, T, Panayi, G.S. New immunological measures of disease activity in rheumatoid arthritis: interleukin 6 and soluble interleukin 2 receptor level in a 6 month trial (abstr). Clin Rheumatol 1990, 9, 121.Google Scholar
  32. 32.
    Sheldon, A., Ahern, M.J., Smith, M.D., Zola, H., Roberts-Thompson, P.J. Response of soluble IL-2 receptor levels during gold therapy for rheumatoid arthritis. Clin Exp Rheumatol 1994, 12, 175–178.PubMedGoogle Scholar
  33. 33.
    Luqmani, R., Sheeran, T., Robinson, M., Richardson, K., Winkles, J., Emery, P. Systemic cytokine measurement: their role in monitoring the response to therapy in patients with rheumatoid arthritis. Clin Exp Rheumatol 1994, 12, 503–508.PubMedGoogle Scholar
  34. 34.
    Crilly, A., McInnes, I.B., Capell, H.A., Madhok, R. The effect of azathioprine on serum levels of interleukin 6 and soluble interleukin 2 receptor. Scand J Rheumatol 1994, 23, 87–91.PubMedGoogle Scholar
  35. 35.
    Kremer, J.M., Stocker, R.P., Rynes, R.I. et al. Methotrexate therapy causes a significant decrease in soluble interleukin 2 receptors in patients with rheumatoid arthritis (abstr). Arthritis Rheum 1991, 35, R37.Google Scholar
  36. 36.
    Dooley, M.A., Cush, J.J., Lipsky, P.E., Dawson, D.V., Pisetsky, D.S. The effect of nonsteroidal antiinflammatory drug therapy in early rheumatoid arthritis on serum levels of soluble interleukin 2 receptor, CD4, and CD8. J Rheumatol 1993, 20, 1857–1862.PubMedGoogle Scholar
  37. 37.
    Kremer, J.M. The mechanism of action of methotrexate in rheumatoid arthritis (Editorial). J Rheumatol 1994, 21, 1–5.PubMedGoogle Scholar
  38. 38.
    Waldmann, T.A., Goldman, C.K., Robb, R.J., et al. Expression of interleukin-2 receptors on activated B-cells. J Exp Med 1984, 160, 1450–1466.PubMedGoogle Scholar
  39. 39.
    Hermann, F., Cannistra, S.A., Levine, H., Griffin, J.D. Expression of interleukin-2 receptors and binding of interleukin-2 by gamma interferon-induced human leukemic and normal monocytic cells. J Exp Med 1985, 162, 1111–1115.PubMedGoogle Scholar
  40. 40.
    Henney, C.S., Kuribayashi, K., Kern, D.S., Gillis, S. Interleukin-2 augments natural killer cell activity. Nature 1981, 291, 335–337.PubMedGoogle Scholar

Copyright information

© Acta Medica Belgica 1995

Authors and Affiliations

  • F. Salaffi
    • 1
  • M. Carotti
    • 1
  • C. Cervini
    • 1
  1. 1.Department of RheumatologyUniversity of AnconaJesi (Ancona)Italy

Personalised recommendations