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The effect of methimazole on the immune system is unlikely to operate directly on T lymphocytes

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Abstract

It has been shown that the antithyroid drug methimazole (MMI) may affect B cells and possibly accessory cell function. In the present study we investigated in detail the effects of MMI on T cell in vitro proliferation. The following variables were evaluated: T cell proliferation following stimulation with phytohemoagglutinin (PHA), and anti-CD3 or anti-CD2 monoclonal antibodies; in-terleukin-2 (IL-2) and gamma-interferon (gamma-IFN) production by PHA-stimulated T cells in bulk culture and by T cell clones; PHA-induced IL-2 receptor expression; LPS-induced interleukin-1 production by accessory cells. The results obtained failed to demonstrate any effect of MMI on T cells in vitro proliferation, whatever the activation pathway considered. In addition, IL-2 and gamma-IFN productions were substantially unaffected by the drug, as well as IL-1 production by accessory cells. However, a slight reduction of PHA-induced IL-2 receptor expression was observed. Although the hypothesis of an effect of MMI on some specialized T cell functions cannot be ruled out, it is likely that the supposed “immunosuppressive” effect of the drug does not concern primarily the T lymphocyte.

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References

  1. Jansson R., Dahlberg P.A., Johansson H., Lindstrom B. Intrathyroidal concentrations of methimazole in patients with Graves’ disease. J. Clin. Endocrinol. Metab. 57: 129, 1983.

    Article  PubMed  CAS  Google Scholar 

  2. Pinchera A., Liberti P., Martino E., Fenzi C.F., Grasso L., Rovis L., Baschieri L. Effects of antithyroid therapy on the long-acting thyroid stimulator and the antithyroglobulin antibodies. J. Clin. Endocrinol. Metab. 29: 231, 1969.

    Article  PubMed  CAS  Google Scholar 

  3. McGregor A.M., Peterson M.M., McLachlan S.M., Rooke P., Smith B.R., Hall R. Carbimazole and the autoimmune response in Graves’ disease. N. Engl. J. Med. 6: 302, 1980.

    Article  Google Scholar 

  4. Romaldini J.H., Rodrigues H., Werner M.C., Bromber N. Graves’ disease and Hashimoto’s thyroiditis: effect of high doses of antithyroid drugs on thyroidal antibodies. J. Steroid Biochem. 20: 1658, 1984.

    Google Scholar 

  5. McLachlan S., Pegg C.A.S., Atherton M.C., Middleton S., Young E.T., Clark F., Smith B.R. The effect of Carbimazole on thyroid autoantibody synthesis by thyroid lymphocytes. J. Clin. Endocrinol. Metab. 60: 1237, 1985.

    Article  PubMed  CAS  Google Scholar 

  6. Weetman A.P., McGregor A.M., Hall R. Methimazole inhibits thyroid autoantibody production by an action on accessory cells. Clin. Immunol. Immunopathol. 28: 39, 1983.

    Article  PubMed  CAS  Google Scholar 

  7. Rennie D.P., McGregor A.M., Keast D., Weetman A.P., Foord S.M., Dieguez C., Williams E.O., Hall R. The influence of methimazole on thyroglobulin-induced autoimmune thyroiditis in the rat. Endocrinology 112: 326, 1983.

    Article  PubMed  CAS  Google Scholar 

  8. Cohen S.B., Weetman A.P. Antithyroid drugs ameliorate thymectomy-induced experimental autoimmune thyroiditis. Autoimmunity 1: 51, 1988.

    Article  PubMed  CAS  Google Scholar 

  9. Weetman A.P., Gunn C., Hall R., McGregor A.M. The absence of any effect of methimazole on in vitro cell-mediated cytotoxicity. Clin. Endocrinol. (Oxf.) 22: 57, 1985.

    Article  CAS  Google Scholar 

  10. Wenzel K.W., Lente J.R. Similar effects of thionamide drugs and Perchlorate on thyroid-stimulating immunoglobulins in Graves’ disease: evidence against an immunosuppressive action of thionamide drugs. J. Clin. Endocrinol. Metab. 58: 62, 1984.

    Article  PubMed  CAS  Google Scholar 

  11. Signore A., Pozzilli P., Di Mario U., Sensi M., Beales P., Andreani D. Inhibition of the receptor for interleukin-2 induced by Carbimazole: relevance for the therapy of autoimmune thyroid disease. Clin. Exp. Immunol. 60: 111, 1985.

    PubMed Central  PubMed  CAS  Google Scholar 

  12. Totterman T.H., Karlsson F.A., Bengtsson M., Mendel Hartvig I. Induction of circulating activated suppressor-like T cells by methimazole therapy for Graves’ disease. N. Engl. J. Med. 316: 15, 1987.

    Article  PubMed  CAS  Google Scholar 

  13. Volpè R. Autoimmune thyroid disease — a perspective. Mol. Biol. Med. 3: 25, 1986.

    PubMed  Google Scholar 

  14. Canonica G.W., Bagnasco M., Kong Y.M. T cell-mediated mechanisms in autoimmune thyroiditis. Immunol. Res. 5: 305, 1986.

    Article  PubMed  CAS  Google Scholar 

  15. Bagnasco M., Venuti D., Prigione I., Torre G.C., Ferrini S., Canonica G.W. Graves’ disease: phenotypic and functional analysis at the clonal level of the T-cell repertoire in peripheral blood and in thyroid. Clin. Immunol. Immunopathol. 47: 230, 1988.

    Article  PubMed  CAS  Google Scholar 

  16. Olive D., Ragueneau M., Cerdan C., Dubreuil P., Lopez M., Mawas C. Anti-CD2 (sheep red blood cell receptor) monoclonal antibodies and T cell activation. Eur. J. Immunol. 16: 1063, 1986.

    Article  PubMed  CAS  Google Scholar 

  17. Moretta A., Pantaleo G., Moretta L., Cerottini J.C., Mingari M.C. Direct demonstration of the clonogenic potential of every human peripheral blood T cell. Clonal analysis of HLA-DR expression and cytolytic activity. J. Exp. Med. 757: 743, 1983.

    Article  Google Scholar 

  18. Bagnasco M., Venuti D., Paolieri F., Torre G.C., Ferrini S., Canonica G.W. Phenotypic and functional analysis at the clonal level of infiltrating T lymphocytes in papillary carcinoma of the thyroid prevalence of cytolytic T cells with Natural-Killer-like or lymphokine-activated killer activity. J. Clin. Endocrinol. Metab. 69: 832, 1989.

    Article  PubMed  CAS  Google Scholar 

  19. Gillis S., Ferm M.M., Ou W., Smith K.A. T cell growth factor: parameters of production and a quantitative microassay for activity. J. Immunol. 720: 2097, 1978.

    Google Scholar 

  20. Weetman A.P., McGregor A.M., Lazarus J.H., Hall R. Thyroid antibodies are produced by thyroid-derived lymphocytes. Clin. Exp. Immunol. 48: 196, 1982.

    PubMed Central  PubMed  CAS  Google Scholar 

  21. McGregor A.M., Ibbertson H.K., Rees Smith B., Hall R. Carbimazole and autoantibody synthesis in Hashimoto’s thyroiditis. Br. Med. J. 207: 968, 1980.

    Article  Google Scholar 

  22. Jansson R., Karesson A., Dahlberg P.A. Thyroxine, methimazole and thyroid microsomal au toantibody titres in hypothyroid Hashimoto’s thyroid itis. Br. Med. J. 290: 11, 1985.

    Article  CAS  Google Scholar 

  23. Weetman A.P., Holt M.E., Campbell A.K., Hall R., McGregor A.M. Methimazole and generation of oxygen radicals by monocytes: potential role in immunosuppression. Br. Med. J. 288: 518, 1984.

    Article  CAS  Google Scholar 

  24. Hallengren B., Forsgren A., Melander A. Effects of antithyroid drugs on lymphocyte function “in vitro”. J. Clin. Endocrinol. Metab. 57: 298, 1980.

    Article  Google Scholar 

  25. Weetman A.P. Effects of the anti-thyroid drug methimazole on interleukin-1 and interleukin-2 levels “in vitro”. Clin. Endocrinol. (Oxf.) 25: 133, 1986.

    Article  CAS  Google Scholar 

  26. Waldmann T.A. Multichain interleukin-2 receptor: a target for immunotherapy in lymphoma. J. Natl. Cancer. Inst. 81: 914, 1989.

    Article  PubMed  CAS  Google Scholar 

  27. Todd I., Pujol-Bourrel R., Hammon L.J., Bottazzo G. Interferon-gamma induces HLA-DR expression by thyroid epithelium. Clin. Exp. Immunol. 61: 265, 1985.

    PubMed Central  PubMed  CAS  Google Scholar 

  28. Bagnasco M., Venuti D., Caria M., Pizzorno G., Ferrini O., Canonica G.W. Methimazole, gamma-interferon and Graves’ disease. In: Pinchera A., Ingbar S.H., McKenzie J.M., Fenzi G.F. (Eds.), Thyroid Autoimmunity. Plenum Press, New York, 1987, p. 445.

    Chapter  Google Scholar 

  29. Aguayo J., Itaka M., Row V.V., Volpè R. Studies of HLA-DR expression on cultured human thyroid: effect of antithyroid drugs and other agents on IFN-gamma-induced HLA-DR expression. J. Clin. Endocrinol. Metab. 66: 903, 1988.

    Article  PubMed  CAS  Google Scholar 

  30. Taniguchi S., Yoshida A., Mashiba H. Direct effect of methimazole on rat thyroidal cell growth induced by thyrotropin and insulin-like growth factor-1. Endocrinology 124: 2046, 1989.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Istituto Scientifico di Medicina Interna, Centro di Immunoendocrinologia and Centro di Allergologia, Università di Genova, 16100, Genova, Italy

    M. Bagnasco M.D., D. Venuti, G. Ciprandi, G. Pesce, F. Paolieri & G. W. Canonica

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  1. M. Bagnasco M.D.
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  2. D. Venuti
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  3. G. Ciprandi
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  4. G. Pesce
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  5. F. Paolieri
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  6. G. W. Canonica
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Bagnasco, M., Venuti, D., Ciprandi, G. et al. The effect of methimazole on the immune system is unlikely to operate directly on T lymphocytes. J Endocrinol Invest 13, 493–499 (1990). https://doi.org/10.1007/BF03348606

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  • DOI: https://doi.org/10.1007/BF03348606

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