Amiodarone stimulates interleukin-6 production in cultured human thyrocytes, exerting cytotoxic effects on thyroid follicles in suspension culture.
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).
Nakajima
K
K
Institute of Clinical Endocrinology, Tokyo Women's Medical University, Japan.
Yamazaki
K
K
Yamada
E
E
Kanaji
Y
Y
Kosaka
S
S
Sato
K
K
Takano
K
K
D000638:Amiodarone / Q000494:pharmacology* / Q000506:poisoning*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D009994:Osmolar Concentration; D011239:Prednisolone / Q000494:pharmacology; D012974:Sodium Iodide / Q000494:pharmacology; D013954:Thyroglobulin / Q000096:biosynthesis; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D013972:Thyrotropin / Q000494:pharmacology; D014284:Triiodothyronine / Q000096:biosynthesis
D005938:Glucocorticoids; D015850:Interleukin-6; D014284:Triiodothyronine; D013972:Thyrotropin; D013954:Thyroglobulin; D011239:Prednisolone; D012974:Sodium Iodide; D000638:Amiodarone