The immunomodulatory effects of anti-thyroid drugs are mediated via actions on thyroid cells, affecting thyrocyte-immunocyte signalling: A review

The mechanism of action of the immunosuppressive effects of antithyroid dru gs has remained a matter of controversy, despite our earlier contention tha t such effects in vivo were indirect; ie., it was our view that the drugs w ere acting on the thyroid cells, reducing their thyroid hormone production and other activities, with a consequent reduction in thyrocyte-immunocyte s ignalling. The reduction in the activation of CD4+ cells,the increased numb er and activation of CD8+ (and CD8+CD11b+) cells, and the reduction of solu ble interleukin-2 receptors, thought once to be direct effects of the medic ation, are now shown to be due to amelioration of the hyperthyroidism. Thus the reduction in thyroid hormone production induced by the drugs is centra l to these actions. In addition, the iodination of thyroglobulin is inhibit ed by these agents, which may affect antigen presentation by the thyrocyte. Furthermore, there is now evidence that the thionamides interfere with thy rocyte expression of such molecules as Class I antigen, interleukin-l, inte rleukin-6, prostaglandin E-2, and heat shock protein. The expression of thy rocyte 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 i n vitro experiments do not corroborate this proposal. In any event, the act ions 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 stimulatin g antibody), the reduced immunological response, and the increased remissio n rate in Graves' disease as a consequence of antithyroid drug therapy, wit hout the need to invoke a direct immunosuppressive effect.