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Interleukin (IL)-12-Driven Primary Hypothyroidism: the Contrasting Roles of Two Th1 Cytokines (IL-12 and Interferon-)

Department of Pathology (H.K., S.-C.T., R.R., M.K., N.R.R., P.C.), The Johns Hopkins School of Medicine, Baltimore, Maryland 21205; Department of Microbiology (K.S.), Leprosy Research Center, National Institute of Infectious Diseases, Tokyo 189-0002, Japan; National Hormone and Peptide Program (A.F.P.), Harbor-University of California at Los Angeles Medical Center, Torrance, California 90509; and Feinstone Department of Molecular Microbiology and Immunology (N.R.R., P.C.), The Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205

Address all correspondence and requests for reprints to: Patrizio Caturegli, Johns Hopkins Pathology, Ross Building, Room 656, 720 Rutland Avenue, Baltimore, Maryland 21205. E-mail: pcat{at}jhmi.edu.

IL-12, a prototypic T helper 1 cytokine, has been implicated in the pathogenesis of organ-specific autoimmune diseases, such as Hashimoto’s thyroiditis, but reported to give conflicting results in murine models of lymphocytic thyroiditis. To determine the effects of chronic, local production of IL-12 within the thyroid gland, we created transgenic mice that express IL-12 p70 under the transcriptional control of the thyroglobulin promoter. Transgenics developed growth retardation, moderate primary hypothyroidism, and mild lymphocytic infiltration of the thyroid gland. The hypothyroidism was associated with increased mRNA levels of the sodium-iodide symporter, an increase partly due to a direct effect of IL-12 on the thyrocyte. Upon immunization with a suboptimal dose of mouse thyroglobulin, IL-12 transgenic mice developed a lymphocytic thyroiditis that was more frequent and severe than that observed in wild-type littermates. The disease-promoting effect of IL-12 was independent of interferon-, as shown by the similar interferon- levels in transgenics and controls. These findings highlight the contrasting roles of two T helper 1 cytokines and report a novel role of IL-12 on thyroid hormonogenesis.

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