Thyroid autoimmunity in patients on long term therapy with leukocyte-derived interferon.
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.
D000328:Adult; D000368:Aged; D001327:Autoimmune Diseases / Q000209:etiology*; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D007370:Interferon Type I / Q000009:adverse effects*; D008134:Long-Term Care; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D008875:Middle Aged; D013960:Thyroid Function Tests; D013961:Thyroid Gland / Q000276:immunology*
D006684:HLA-DR Antigens; D007370:Interferon Type I