Amiodarone stimulates interleukin-6 production in cultured human thyrocytes, exerting cytotoxic effects on thyroid follicles in suspension culture

Citation
K. Nakajima et al., Amiodarone stimulates interleukin-6 production in cultured human thyrocytes, exerting cytotoxic effects on thyroid follicles in suspension culture, THYROID, 11(2), 2001, pp. 101-109
Citations number
33
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
THYROID
ISSN journal
1050-7256 → ACNP
Volume
11
Issue
2
Year of publication
2001
Pages
101 - 109
Database
ISI
SICI code
1050-7256(200102)11:2<101:ASIPIC>2.0.ZU;2-E
Abstract
To investigate whether amiodarone increases interleukin-6 (IL-6) production in thyrocytes, human follicles obtained from subtotally thyroidectomized p atients with Graves' disease were cultured in serum-free medium supplemente d with various concentrations of bovine thyrotropin (bTSH) and amiodarone. The follicles gradually formed monolayer cells and secreted triiodothyronin e (T-3), thyroglobulin (Tg), and IL-6 for at least 14 days. TSH dose-depend ently increased T-3 and Tg but not IL-6 levels in the conditioned medium. A miodarone exerted no significant effect on T-3, Tg, or IL-6 concentrations at 0.1-1 muM. In contrast, at 10-20 muM, it decreased T-3 and Tg, but incre ased IL-6 levels, and these changes were accompanied by increased expressio n of IL-6 mRNA. Amiodarone-induced IL-6 production was inhibited by prednis olone at 10(-7) M. Electron microscopic examination revealed that the thyro id follicles in the suspension culture remained intact at 1 muM, but that c ytotoxic effects (decreased microvilli and increased onion-like inclusion b odies) occurred at higher concentrations (10-25 muM). These in vitro findin gs indicate that amiodarone does not impair thyroid function at clinically attainable serum levels (1 muM), but exerts cytotoxic effect by inducing th e 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).