title: Evidence that the immunosuppressive effects of antithyroid drugs are mediated through actions on the thyroid cell, modulating thyrocyte-immunocyte signaling: a review.
abstract: 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, i.e., it was our view that the drugs were acting on the thyroid cells, reducing their hormone production and other activities, with a consequent reduction in thyrocyte-immunocyte signaling. The reduction in the activation of CD4+ cells, the increased number and activation of CD8+ (and CD8+CDIIb+) 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 Class I antigen, interleukin-1, interleukin-6, prostaglandin E2, 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 antithyroid drugs on the thyroid cells, 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, without the need to invoke a direct immunosuppressive effect.
authors.affiliation: Department of Medicine, Wellesley Hospital, University of Toronto, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Volpé
mesh_terms: D000906:Antibodies / Q000032:analysis; D013956:Antithyroid Agents / Q000494:pharmacology* / Q000627:therapeutic use; D006111:Graves Disease / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007107:Immune System / Q000187:drug effects*; D007108:Immune Tolerance; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects*; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology*
chemical_list: D000906:Antibodies; D013956:Antithyroid Agents