Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05231 (interleukin-6)
 23,907 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 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 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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PMID:The immunomodulatory effects of anti-thyroid drugs are mediated via actions on thyroid cells, affecting thyrocyte-immunocyte signalling: a review. 1128 52

To investigate whether amiodarone increases interleukin-6 (IL-6) production in thyrocytes, human follicles obtained from subtotally thyroidectomized patients with Graves' disease were cultured in serum-free medium supplemented with various concentrations of bovine thyrotropin (bTSH) and amiodarone. The follicles gradually formed monolayer cells and secreted triiodothyronine (T3), thyroglobulin (Tg), and IL-6 for at least 14 days. TSH dose-dependently increased T3 and Tg but not IL-6 levels in the conditioned medium. Amiodarone exerted no significant effect on T3, Tg, or IL-6 concentrations at 0.1-1 microM. In contrast, at 10-20 microM, it decreased T3 and Tg, but increased IL-6 levels, and these changes were accompanied by increased expression of IL-6 mRNA. Amiodarone-induced IL-6 production was inhibited by prednisolone at 10(-7) M. Electron microscopic examination revealed that the thyroid follicles in the suspension culture remained intact at 1 microM, but that cytotoxic effects (decreased microvilli and increased onion-like inclusion bodies) occurred at higher concentrations (10-25 microM). These in vitro findings indicate that amiodarone does not impair thyroid function at clinically attainable serum levels (1 microM), but exerts cytotoxic effect by inducing the production of a proinflammatory cytokine (IL-6) at higher concentrations. Because amiodarone-induced IL-6 production was inhibited by prednisolone, it is reasonable to administer glucocorticoids to patients with amiodarone-induced destructive thyrotoxicosis (type II).
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PMID:Amiodarone stimulates interleukin-6 production in cultured human thyrocytes, exerting cytotoxic effects on thyroid follicles in suspension culture. 1128 78

We explored the role of interleukin-6 (IL-6) in the development of autoimmune thyroiditis in nonobese diabetic (NOD) mice, an animal model of Hashimoto's thyroiditis, using anti-mouse IL-6 receptor antibody (MR16-1). Thyroiditis was induced by iodide ingestion or mouse thyroglobulin (Tg) immunization. Mice were injected intraperitoneally with saline, control rat IgG, or MR16-1 (2 or 8 mg). Iodide ingestion did not increase serum IL-6 levels and MR16-1 (2 mg) failed to prevent the development of thyroiditis. In contrast, Tg immunization induced a rapid and significant increase in serum IL-6 levels. While MR16-1 (2 mg) had no effect on Tg-induced thyroiditis, the severity, but not incidence, of thyroiditis was reduced in 8 mg MR16-1-treated mice compared with saline-injected mice. However, thyroiditis development in the 8 mg MR16-1-treated mice was indistinguishable from that in the control IgG-treated mice. MR16-1 (8 mg) did not affect serum anti-Tg antibody levels. These results suggest that IL-6 may play only a minor role in the development of autoimmune thyroiditis in NOD mice.
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PMID:Effects of interleukin-6 blockade on the development of autoimmune thyroiditis in nonobese diabetic mice. 1930 Dec 5


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