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
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).