INTERLEUKIN-6 INHIBITS HUMAN THYROID PEROXIDASE GENE-EXPRESSION

It has been reported that cytokines, especially interleukin 1 and interferon-gamma, inhibit the thyroid hormone secretion and the gene expression of human thyroid peroxidase and thyroglobulin. Interleukin 6 has recently been found to be an important cytokine for the regulation of immunoendocrine interaction and intrathyroidal production of interleukin 6 has been reported. Therefore, we investigated the regulation of thyroid hormone secretion and thyroid peroxidase messenger RNA by interleukin 6 in human thyrocytes to clarify further the functional role of interleukin 6 in thyroid glands. Thyrocytes dispersed from Graves' thyroid tissues were incubated with TSH with or without interleukin 6. TSH (5 U/l) stimulated the expression of thyroid peroxidase mRNA transcripts (4.0, 3.2, 2.1, and 1.7 kb, respectively), although unstimulated thyrocytes contained the low level of 3.2 kb thyroid peroxidase mRNA transcript. Interleukin 6 (10(4)-10(5) U/l) inhibited TSH-induced thyroid peroxidase mRNA in a dose-dependent manner, although the basal level of thyroid peroxidase mRNA expression was not suppressed by interleukin 6. Interleukin 6 also inhibited 8-bromo-cyclic adenosine monophosphate-induced thyroid peroxidase mRNA levels. In contrast, the gamma-action mRNA hybridization signal was not altered in control or treated cells. Subsequently, interleukin 6 inhibited TSH-induced T3 secretion in a dose-dependent manner after 72 h treatment. However, interleukin 6 did not affect DNA synthesis. Pretreatment with specific antibody against interleukin 6 selectively restored the inhibitory effect of interleukin 6 on thyroid peroxidase gene expression. Our results suggest that interleukin 6 plays an inhibitory role in the thyroid gland, in addition to interleukin 1 and interferon-gamma.