EFFECT OF GLUCOCORTICOIDS AND ESTROGEN ON INTERLEUKIN-6 PRODUCTION BYHUMAN THYROCYTES FROM PATIENTS WITH GRAVES-DISEASE AND TOXIC MULTINODULAR GOITER AND FROM HTORI3 CELLS

Interleukin-6 (IL-6) is a cytokine released by thyrocytes and is invol ved in disease processes such as autoimmune thyroid disease. The secre tion of IL-6 can be stimulated by interleukin-1 (IL-1), tumour necrosi s factor-alpha (TNF), serum, TSH and agents which increase intracellul ar cyclic BMP levels. Antithyroid drugs such as methimazole inhibit IL -6 production by thyrocytes but the effects of glucocorticoids and oes trogen have not been investigated. The effects of dexamethasone and 17 beta-oestradiol on IL-1-, TNF-, TSH-, forskolin-and phorbol 12-myrist ate 13-acetate (PMA)-stimulated IL-6 release in serum-free conditions were studied in human thyrocytes derived from patients with Graves' di sease and toxic multinodular goitres, and in the immortalised human th yrocyte cell line, HTori3. Dexamethasone inhibited IL-6 production und er stimulated conditions. In serum-free conditions, no basal release o f IL-6 was assayable. In all but one of the primary thyroid cultures, TSH did not stimulate IL-6 release above the lower detectable limit of the assay. In Graves' and multinodular goitre thyrocytes, inhibition of IL-1 (100 U/ml)-stimulated IL-6 release by dexamethasone (100 nmol/ l) was 62.51%+/-10.43 (S.E.M.), and in HTori3 cells it was 78.35%+/-3. 9. The degree of IL-1 stimulation of IL-6 release and inhibition by de xamethasone was not significantly different in thyrocytes derived from either Graves' or multinodular glands. 17 beta-oestradiol had no effe ct on IL-1-stimulated IL-6 release in either primary thyroid cell cult ure or in HTori3 cells.