RELEASE OF INTERLEUKIN-6 BY HUMAN THYROID EPITHELIAL-CELLS IMMORTALIZED BY SIMIAN VIRUS-40 DNA TRANSFECTION

Interleukin-6 (IL-6) has actions on a variety of endocrine tissues. The cytokine is secreted by cells of the anterior pituitary and endocrine pancreas and has recently been shown to be produced by cultures of thyroid epithelial cells. In this study we have examined some of the factors which regulate IL-6 release from an immortalized human thyroid line (HTori3). IL-6 release over 24 h was stimulated by TSH (5000-mu-U/ml), by forskolin (0.01 mmol/l), by fetal calf serum (1-20%) and by epidermal growth factor (20 ng/ml). Stimulation was also apparent with gamma-interferon and with tumour necrosis factor at concentrations known to enhance class II major histocompatibility antigen expression by thyroid epithelium. The most potent factor tested was interleukin-1 (IL-1). which controls IL-6 release from other cell types. Threefold stimulation was found with 1 U/ml rising to 350-fold with 1000 U/ml. The effect of IL-1 took 2 h to develop and was blocked by cycloheximide (100-mu-mol/l). Stimulation was not markedly inhibited by pertussis toxin. Many of the actions of IL-1 are mediated by prostaglandin E2 (PGE2). At concentrations as low as 30 nmol/l, PGE2 stimulated IL-6 release but the maximum stimulation obtained with PGE, was only threefold. The effect of IL-1 was not inhibited by indomethacin. These data provide further evidence that IL-6 is produced by human thyrocytes. The effect of IL-1 has not been demonstrated previously. Stimulation of IL-6 release by IL-1 did not appear to be mediated by prostaglandin. IL-6 may influence hormone release from the thyroid as it does in other tissues. High concentrations of IL-6 in the thyroid may increase infiltration by, and activation of, lymphocytes in patients with autoimmune thyroid disease.