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The Immunomodulatory Effects of Anti-thyroid Drugs are Mediated via Actions on Thyroid Cells, Affecting Thyrocyte-immunocyte Signalling A Review

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The mechanism of action of the immunosuppressive effects of antithyroid drugs has remained a matter of controversy, despite our earlier contention that such effects in vivo were indirect ie., it was our view that the drugs were acting on the thyroid cells, reducing their thyroid hormone production and other activities, with a consequent reduction in thyrocyte-immunocyte signalling. The reduction in the activation of CD4+ cells,the increased number and activation of CD8+ (and CD8+CDllb+) cells, and the reduction of soluble interleukin-2 receptors, thought once to be direct effects of the medication, are now shown to be due to amelioration of the hyperthyroidism. Thus the reduction in thyroid hormone production induced by the drugs is central to these actions. In addition, the iodination of thyroglobulin is inhibited by these agents, which may affect antigen presentation by the thyrocyte. Furthermore, there is now evidence that the thionamides interfere with thyrocyte expression of such molecules as Class I antigen, interleukin 1 , interleukin-6, prostaglandin E 2 , and heat shock protein. The expression of thyrocyte Class II antigen is probably not inhibited by these drugs, although one group has shown that lectin-stimulated thyrocyte Class II expression is diminished by this treatment this group postulated that this effect might be mediated by reduced interferon gamma production by T lymphocytes, but in vitro experiments do not corroborate this proposal. In any event, the actions as described of the effects of antithyroid drugs on the thyroid cells (particularly normalization of thyroid function) would certainly suffice to explain the diminution of thyroid antibodies (including thyroid stimulating antibody), the reduced immunological response, and the increased remission rate in Graves disease as a consequence of antithyroid drug therapy, without the need to invoke a direct immunosuppressive effect.
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Keywords: Anti-thyroid Drugs; Graves disease; Grubeck Loebenstein; Immunomodulatory Effects; Soluble interleukin; Thyrocyte immunocyte Signalling; Thyroid Antibodies; immunosuppressive; interferon gamma production; lectin stimulated thyrocyte; thyroperoxidase

Document Type: Review Article

Publication date: April 1, 2001

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  • Current Pharmaceutical Design publishes timely in-depth reviews covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area. A Guest Editor who is an acknowledged authority in a therapeutic field has solicits for each issue comprehensive and timely reviews from leading researchers in the pharmaceutical industry and academia.

    Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design, including: medicinal chemistry, pharmacology, drug targets and disease mechanism.
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