Thyroid Autoimmunity in Patients on Long Term Therapy with Leukocyte-Derived Interferon*

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Abstract
Among 49 patients with carcinoid tumors given long term therapy (mean, 8 months; range, 3-36) with human leukocyte-derived interferon-a (huLe-IFNa), hypothyroidism occurred in 5 andthyrotoxicosis 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 aferthe 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 withthe huLe-IFNa preparation induced a rise in activated T-helper and T-suppressor cells. This effect was mimicked by recombinant IFN7 (r-IFN7), but not by r-IFNa. Further, the huLe-IFNa preparation employed induced HLA-DR expression on human thyroid cells in tissue culture as did T-IFNY, but not r-IFNa, suggesting the presence of bioactive IFN7 in the huLe-IFNa preparation. The results demonstrate that thyroid autoimmune disease can occur as a side-effect of treatment with huLe-IFNa and suggest that IFNs may play important regulatory roles, at both the effector and target cell levels, in the development of human autoimmune disorders. (J ClinEndocrinolMetab63:1086,1986)

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