Inhibition of¹²⁵I Organification and Thyroid Hormone Release by Interleukin-1, Tumor Necrosis Factor-α, and Interferon-γin Human Thyrocytes in Suspension Culture*

Abstract

To elucidate the mechanism of decreased 131I uptake by the thyroid gland in patients with subacute thyroiditis and painless thyroiditis, human thyroid follicles were cultured with interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF alpha), and/or interferon-gamma (IFN gamma), and the effects of these cytokines on thyroid function were studied in vitro. When human thyrocytes were cultured in RPMI-1640 medium containing 0.5% fetal calf serum and TSH for 5-8 days, the cells incorporated 125I, synthesized de novo [125I]iodotyrosines and [125I]iodothyronines, and secreted [125I]T4 and [125I]T3 into the medium. IL-1 alpha and IL-1 beta inhibited 125I incorporation and [125I]iodothyronine release in a concentration-dependent manner. The minimal inhibitory effect was detected at 10 pg/ml. Electron microscopic examination revealed a marked decrease in lysosome formation in IL-1-treated thyrocytes. TNF alpha and IFN gamma also inhibited thyroid function in a concentration-dependent manner. Furthermore, when thyrocytes were cultured with IL-1, TNF alpha and IFN gamma, these cytokines more than additively inhibited thyroid function. Although the main mechanism of 131I uptake suppression in the thyroid gland in subacute thyroiditis is due to cellular damage and suppression of TSH release, our present findings suggest that IL-1, TNF alpha, and IFN gamma produced in the inflammatory process within the thyroid gland further inhibit iodine incorporation and at least partly account for the decreased 131I uptake by the thyroid gland in destruction-induced hyperthyroidism.

Increased serum interleukin‐1bT during treatment of zhyperthyroidism with antithyroid drugs

“…Thus, in vitro studies have shown that IL-lp inhibits '251-organification and thyroid hormone production by cultured human thyrocytes [8,9]. Also relevant in this context is the suggestion that IL-lp as well as TNF-(r and IFN-y produced locally by immunoregulatory cells in the process of thyroid inflammation may be, at least in part, responsible for the decreased 1 3 1 I-uptake in the thyroid gland of patients with subacute thyroiditis [28].…”

“…With regard to thyroid function, IL-I has been shown to inhibit 1251-organification, as well as thyroid hormone, thyroglobulin and CAMP production in cultured human thyrocytes [8,9]. Furthermore, IL-1 is found in thyroid tissues and receptors for IL-I are present in thyroid cells [10,1 I].…”

The clinical and physiological spectrum of interferon-alpha induced thyroiditis: Toward a new classification

“…90 Thyroid cells have been shown to have specific binding sites for IL-6, 85 which decreases TSH-mediated iodine uptake and thyroid hormone release . 85,91 In addition, IFN␣ has been shown in some studies to modify immunoglobulin production and to decrease T regulatory cell function. 92,93 A greater incidence of Th1 activity has been demonstrated in organ specific autoimmunity.…”

Vascular Endothelial Growth Factors and Thyroid Disorders.

“…In agarose-coated dishes, thyroid follicles cannot attach to the bottom of culture dishes and can be cultured in suspension for a couple of weeks maintaining thyroid function such as 1251 incorporation and release of de novo synthesized thyroid hormones (1251-T3 + 125I-T4) into the culture medium ( Fig. 2) [10][11][12]. When thyroid follicles were cultured in the presence of TSH for a couple of days, steady state mRNA levels of VEGF were increased several fold in thyroid follicles cultured in low concentrations of fetal bovine serum (0.5%) (Fig.…”