Effect of tumor necrosis factor on growth and function in FRTL5 cells

Tumor necrosis factor (TNF) is a cytokine produced by inflammatory macrophages and monocytes. FRTL5 cells are a continuous line of functional, nontransformed rat thyroid cells that depend on thyroid-stimulating hormone (TSH) for sustained growth. The following experiments characterize the effects of TNF on growth and differentiated functions in FRTL5 cells. Cells were incubated with different concentrations of TNF (1 to 100 ng/ml), alone or with TSH. FRTL5 cell proliferation was assessed by 3H-thymidine incorporation assays. Differentiated functions were studied by measuring radioactive iodine uptake (RAI) and triiodothyronine (T3) production. TNF inhibited FRTL5 cell growth both in basal conditions and after cells had been exposed to TSH. TNF caused small inhibition of both basal RAI uptake and T3 release but greatly decreased TSH-stimulated RAI uptake and T3 secretion. In summary, TNF appears to affect both growth and differentiated functions in the FRTL5 cell line. Although it is difficult to extrapolate these in vitro results to the human disease state, we postulate that TNF production in septic states may contribute to the pathogenesis of the low T3 syndrome; moreover, locally produced TNF may modulate thyroid function in autoimmune thyroid diseases.