This Article Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by SATO, K. Articles by KANAJI, Y. Search for Related Content PubMed PubMed Citation Articles by SATO, K. Articles by KANAJI, Y.

Inhibition of ¹²⁵I Organification and Thyroid Hormone Release by Interleukin-1, Tumor Necrosis Factor-, and Interferon- in Human Thyrocytes in Suspension Culture^*

Departments of Medicine (K.Sa., M.O., H.I., T.T., H.D.) and Endocrine Surgery (Yoshiha, K, Y.I., T.O., Y.F.) Institute of Clinical Endocrinology, Tokyo Women's Medical College Kawada-cho 8-1, Shinjuku-ku
Research Institute of the Foundation for Growth Science in Japan (T.S., K.Sh.) Wakamatsu-cho, Shinjukuku
Kanaji Hospital (Y.K.), and Saitama Medical College (D.C.) Kawagoe, Saitama-ken, Japan

Address requests for reprints to: Dr. Kanji Sato, Department of Medicine, Institute of Clinical Endocrinology, Tokyo Women's Medical College, Kawada-cho 8-1, Shinjuku-ku, Tokyo 162, Japan.

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 - (TNF), and/or interferon - (IFN), 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-l and IL-β 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 and IFN also inhibited thyroid function in a concentration-dependent manner. Furthermore, when thyrocytes were cultured with IL-1, TNF and IFN, 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, and IFN 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.

^* Presented in part at the 59th Meeting of the Japanese Endocrine Society, November 1987, Tokyo, Japan, and the 8th International Congress of Endocrine Society (Abstract 12-18-014), July 1988, Kyoto, Japan. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan (no. 61570563), the Kato Memorial Trust for Nambyo Research, and a research grant from the Foundation for Growth Science in Japan.

Received November 13, 1989.

This article has been cited by other articles:

				K. Yamazaki, K. Suzuki, E. Yamada, T. Yamada, F. Takeshita, M. Matsumoto, T. Mitsuhashi, T. Obara, K. Takano, and K. Sato Suppression of Iodide Uptake and Thyroid Hormone Synthesis with Stimulation of the Type I Interferon System by Double-Stranded Ribonucleic Acid in Cultured Human Thyroid Follicles Endocrinology, July 1, 2007; 148(7): 3226 - 3235. [Abstract] [Full Text] [PDF]

				N. Caraccio, R. Giannini, S. Cuccato, P. Faviana, P. Berti, D. Galleri, A. Dardano, F. Basolo, E. Ferrannini, and F. Monzani Type I Interferons Modulate the Expression of Thyroid Peroxidase, Sodium/Iodide Symporter, and Thyroglobulin Genes in Primary Human Thyrocyte Cultures J. Clin. Endocrinol. Metab., February 1, 2005; 90(2): 1156 - 1162. [Abstract] [Full Text] [PDF]

				C. Carella, G. Mazziotti, G. Amato, L. E. Braverman, and E. Roti Interferon-{alpha}-Related Thyroid Disease: Pathophysiological, Epidemiological, and Clinical Aspects J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3656 - 3661. [Full Text] [PDF]

				M. Ohmori, N. Harii, T. Endo, and T. Onaya Tumor Necrosis Factor-{alpha} Regulation of Thyroid Transcription Factor-1 and Pax-8 in Rat Thyroid FRTL-5 Cells Endocrinology, October 1, 1999; 140(10): 4651 - 4658. [Abstract] [Full Text]

				A. Miyazaki, H. Shimura, T. Endo, K. Haraguchi, and T. Onaya Tumor Necrosis Factor-{alpha} and Interferon-{gamma} Suppress Both Gene Expression and Deoxyribonucleic Acid-Binding of TTF-2 in FRTL-5 Cells Endocrinology, September 1, 1999; 140(9): 4214 - 4220. [Abstract] [Full Text]

				K. Tornquist, A.-M. Malm, M. Pasternack, R. Kronqvist, S. Bjorklund, R. Tuominen, and J. P. Slotte Tumor Necrosis Factor-alpha , Sphingomyelinase, and Ceramide Inhibit Store-operated Calcium Entry in Thyroid FRTL-5 Cells J. Biol. Chem., April 2, 1999; 274(14): 9370 - 9377. [Abstract] [Full Text] [PDF]

				T. van der Poll, E. Endert, S. M. Coyle, J. M. Agosti, and S. F. Lowry Neutralization of TNF does not influence endotoxininduced changes in thyroid hormone metabolism in humans Am J Physiol Regulatory Integrative Comp Physiol, February 1, 1999; 276(2): R357 - R362. [Abstract] [Full Text] [PDF]

				L. J. De Groot Dangerous Dogmas in Medicine: The Nonthyroidal Illness Syndrome J. Clin. Endocrinol. Metab., January 1, 1999; 84(1): 151 - 164. [Full Text]

				M. Nilsson, J. Husmark, U. Björkman, and L. E. Ericson Cytokines and Thyroid Epithelial Integrity: Interleukin-1{alpha} Induces Dissociation of the Junctional Complex and Paracellular Leakage in Filter-Cultured Human Thyrocytes J. Clin. Endocrinol. Metab., March 1, 1998; 83(3): 945 - 952. [Abstract] [Full Text]

				A. E. Pekary, J. M. Hershman, and L. Berg Tumor Necrosis Factor, Ceramide, Transforming Growth Factor-{beta}1, and Aging Reduce Na+/I- Symporter Messenger Ribonucleic Acid Levels in FRTL-5 Cells Endocrinology, February 1, 1998; 139(2): 703 - 712. [Abstract] [Full Text] [PDF]

				K. Sato, M. Miyakawa, N. Onoda, H. Demura, T. Yamashita, M. Miura, T. Kasajima, K. Yamazaki, and T. Obara Increased Concentration of Vascular Endothelial Growth Factor/Vascular Permeability Factor in Cyst Fluid of Enlarging and Recurrent Thyroid Nodules J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1968 - 1973. [Abstract] [Full Text] [PDF]

				I. J. Chopra Euthyroid Sick Syndrome: Is It a Misnomer? J. Clin. Endocrinol. Metab., February 1, 1997; 82(2): 329 - 334. [Full Text] [PDF]