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 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).

• Authors: K Nakajima, K Yamazaki, E Yamada, Y Kanaji, S Kosaka, K Sato, K Takano
• Journal: Thyroid : official journal of the American Thyroid Association (Thyroid) Vol. 11 Issue 2 Pg. 101-9 (Feb 2001) ISSN: 1050-7256 [Print] United States
• PMID: 11288978 (Publication Type: Journal Article)

Chemical References

• Glucocorticoids
• Interleukin-6
• Triiodothyronine
• Thyrotropin
• Thyroglobulin
• Prednisolone
• Sodium Iodide
• Amiodarone

Topics

• Amiodarone (pharmacology, poisoning)
• Animals
• Cattle
• Cells, Cultured
• Glucocorticoids (pharmacology)
• Humans
• Interleukin-6 (biosynthesis)
• Osmolar Concentration
• Prednisolone (pharmacology)
• Sodium Iodide (pharmacology)
• Thyroglobulin (biosynthesis)
• Thyroid Gland (cytology, drug effects, metabolism, pathology)
• Thyrotropin (pharmacology)
• Triiodothyronine (biosynthesis)