Journal of Clinical Endocrinology & Metabolism, Vol 63, 1086-1090, Copyright © 1986 by Endocrine Society

ARTICLES

Thyroid autoimmunity in patients on long term therapy with leukocyte- derived interferon

P Burman, TH Totterman, K Oberg and FA Karlsson

Among 49 patients with carcinoid tumors given long term therapy (mean, 8 months; range, 3-36) with human leukocyte-derived interferon-alpha (huLe-IFN alpha), hypothyroidism occurred in 5 and thyrotoxicosis in 2. Antibodies against thyroid microsomal antigen and/or thyroglobulin were found in 13 patients. In 7 of these, 3 of whom developed hypothyroidism, the antibodies appeared after the start of therapy. During treatment, an increase in the proportions of circulating activated surface HLA-DR-positive T-helper and T-suppressor cells occurred after 3-4 days, and the proportions remained elevated at 3 and 6 months. Incubation of T cells of normal individuals in vitro with the huLe-IFN alpha preparation induced a rise in activated T-helper and T- suppressor cells. This effect was mimicked by recombinant IFN gamma (r- IFN gamma), but not by r-IFN alpha. Further, the huLe-IFN alpha preparation employed induced HLA-DR expression on human thyroid cells in tissue culture as did r-IFN gamma, but not r-IFN alpha, suggesting the presence of bioactive IFN gamma in the huLe-IFN alpha preparation. The results demonstrate that thyroid autoimmune disease can occur as a side-effect of treatment with huLe-IFN alpha and suggest that IFNs may play important regulatory roles, at both the effector and target cell levels, in the development of human autoimmune disorders.

This article has been cited by other articles:

				M. Rotondi, R. Minelli, F. Magri, P. Leporati, P. Romagnani, M. C. Baroni, R. Delsignore, M. Serio, and L. Chiovato Serum CXCL10 levels and occurrence of thyroid dysfunction in patients treated with interferon-{alpha} therapy for hepatitis C virus-related hepatitis Eur. J. Endocrinol., April 1, 2007; 156(4): 409 - 414. [Abstract] [Full Text] [PDF]

				N. Harii, C. J. Lewis, V. Vasko, K. McCall, U. Benavides-Peralta, X. Sun, M. D. Ringel, M. Saji, C. Giuliani, G. Napolitano, et al. Thyrocytes Express a Functional Toll-Like Receptor 3: Overexpression Can Be Induced by Viral Infection and Reversed by Phenylmethimazole and Is Associated with Hashimoto's Autoimmune Thyroiditis Mol. Endocrinol., May 1, 2005; 19(5): 1231 - 1250. [Abstract] [Full Text] [PDF]

				Z.-X. Lian, K. Kikuchi, G.-X. Yang, A. A. Ansari, S. Ikehara, and M. E. Gershwin Expansion of Bone Marrow IFN-{alpha}-Producing Dendritic Cells in New Zealand Black (NZB) Mice: High Level Expression of TLR9 and Secretion of IFN-{alpha} in NZB Bone Marrow J. Immunol., October 15, 2004; 173(8): 5283 - 5289. [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]

				E. Jonasch and F. G. Haluska Interferon in Oncological Practice: Review of Interferon Biology, Clinical Applications, and Toxicities Oncologist, February 1, 2001; 6(1): 34 - 55. [Abstract] [Full Text]

				M. Pelegrin, J. C. Devedjian, C. Costa, J. Visa, G. Solanes, A. Pujol, G. Asins, A. Valera, and F. Bosch Evidence from Transgenic Mice That Interferon-beta May Be Involved in the Onset of Diabetes Mellitus J. Biol. Chem., May 15, 1998; 273(20): 12332 - 12340. [Abstract] [Full Text] [PDF]

				S.-C. J. Yeung, A. C. Chiu, R. Vassilopoulou-Sellin, and R. F. Gagel The Endocrine Effects of Nonhormonal Antineoplastic Therapy Endocr. Rev., April 1, 1998; 19(2): 144 - 172. [Abstract] [Full Text]

				S.-I. Taniguchi, M. Shong, C. Giuliani, G. Napolitano, M. Saji, V. Montani, K. Suzuki, D. S. Singer, and L. D. Kohn Iodide Suppression of Major Histocompatibility Class I Gene Expression in Thyroid Cells Involves Enhancer A and the Transcription Factor NF-{kappa}B Mol. Endocrinol., January 1, 1998; 12(1): 19 - 33. [Abstract] [Full Text]

				C. M. Dayan and G. H. Daniels Chronic Autoimmune Thyroiditis N. Engl. J. Med., July 11, 1996; 335(2): 99 - 107. [Full Text] [PDF]

				M.A. Abdul-Jabbar, R.M. Ehrlich, N. Mann, and E.A. Roberts Transient Hypothyroidism in a Child Treated With Alpha-Interferon for Chronic Hepatitis B Infection Clinical Pediatrics, December 1, 1995; 34(12): 663 - 665. [PDF]

				M. J. Fritzler Drugs Recently Associated With Lupus Syndromes Lupus, December 1, 1994; 3(6): 455 - 459. [Abstract] [PDF]

				D. Kausman and D.A. Isenberg Role of the Biologics in Autoimmunity Lupus, December 1, 1994; 3(6): 461 - 466. [PDF]

				T. Stewart, B Hultgren, X Huang, S Pitts-Meek, J Hully, and N. MacLachlan Induction of type I diabetes by interferon-alpha in transgenic mice Science, June 25, 1993; 260(5116): 1942 - 1946. [Abstract] [PDF]