INVITRO EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA ON HUMAN THYROID FOLLICULAR CELLS

Tumor necrosis factor-alpha is assumed to be an important mediator in thyroid autoimmunity. In the present study we have shown that human thyrocytes possess a single specific binding site for recombinant tumor necrosis factor-alpha with an average of 9,300 receptors/cell (K(d) = 1.9 . 10(-10) mol). The effects of the cytokine on thyroid cell proliferation were assessed by H-3-thymidine uptake as well as by the protein and DNA content of cell monolayers. Low dose tumor necrosis factor-alpha resulted in a moderate stimulation of cell proliferation with an increase of H-3-thymidine incorporation from 44,613 +/- 7,989 cpm under basal conditions to 63,326 +/- 6,822 cpm after 100 U/l tumor necrosis factor-alpha (p < 0.0 1). Higher doses of the cytokine were less effective. On average, bTSH stimulated cAMP production of human thyrocytes was significantly augmented after preincubation with recombinant tumor necrosis factor-alpha. The maximum effect was observed after 1,000 U/l tumor necrosis factor-alpha (281.5 +/- 107.0 vs 114.5 +/- 33.6 fmol cAMP/mug protein under basal conditions; p < 0.05), whereas higher doses of the cytokine were again less effective. This phenomenon could at least partly be explained by a cytokine-mediated downregulation of tumor necrosis factor-alpha binding. We conclude that in vitro tumor necrosis factor-alpha modulates in addition to its well known synergistic effect on interferon-gamma induced HLA class II expression the function and proliferation of human thyroid follicular cells as well. These effects are mediated via specific cell surface receptors;