Amiodarone Stimulates Interleukin-6 Production in Cultured Human Thyrocytes,Exerting Cytotoxic Effects on Thyroid Follicles in Suspension Culture

Abstract

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 μM. In contrast, at 10-20 μM, 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 μM, but that cytotoxic effects (decreased microvilli and increased onion-like inclusion bodies) occurred at higher concentrations (10-25 μM). These in vitro findings indicate that amiodarone does not impair thyroid function at clinically attainable serum levels (1 μM), 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).