Effect of glucocorticoids and oestrogen on interleukin-6 production by human thyrocytes from patients with Graves' disease and toxic multinodular goitre and from HTori3 cells.
Interleukin-6 (IL-6) is a cytokine released by thyrocytes and is involved in disease processes such as autoimmune thyroid disease. The secretion of IL-6 can be stimulated by interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF), serum, TSH and agents which increase intracellular cyclic AMP levels. Antithyroid drugs such as methimazole inhibit IL-6 production by thyrocytes but the effects of glucocorticoids and oestrogen have not been investigated. The effects of dexamethasone and 17 beta-oestradiol on IL-1-, TNF-, TSH-, forskolin- and phorbol 12-myristate 13-acetate (PMA)-stimulated IL-6 release in serum-free conditions were studied in human thyrocytes derived from patients with Graves' disease and toxic multinodular goitres, and in the immortalised human thyrocyte cell line, HTori3. Dexamethasone inhibited IL-6 production under stimulated conditions. In serum-free conditions, no basal release of 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 dexamethasone was not significantly different in thyrocytes derived from either Graves' or multinodular glands. 17 beta-Oestradiol had no effect on IL-1-stimulated IL-6 release in either primary thyroid cell culture or in HTori3 cells.
Jones
T H
TH
University Department of Medicine, Northern General Hospital, Sheffield, UK.
Kennedy
R L
RL
Justice
S K
SK
Davies
R
R
D002461:Cell Line, Transformed; D003907:Dexamethasone / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006044:Goiter, Nodular / Q000378:metabolism* / Q000473:pathology; D006111:Graves Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D013268:Stimulation, Chemical; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism* / Q000473:pathology
D005938:Glucocorticoids; D015850:Interleukin-6; D004958:Estradiol; D003907:Dexamethasone