INTERLEUKIN-1 INHIBITS HUMAN THYROID-CARCINOMA CELL-GROWTH

In order to further clarify the growth regulating effect of cytokines on thyroid cell proliferation, the effect of interleukin-1 (IL-1) was tested on growth of human papillary and follicular thyroid carcinoma cells (NPA and WRO). Although fetal bovine serum stimulated DNA synthesis, TSH did not affect cell growth and the level of thyroglobulin messenger RNA (mRNA) in NPA. Eight-bromo-cAMP and forskolin, however, significantly suppressed DNA synthesis, suggesting the impairment of TSH receptor signal transduction in NPA cells despite of the presence of [I-125]TSH binding. Both IL-1-alpha and beta inhibited [H-3] thymidine uptake into NPA cell DNA in a dose- and time-dependent manner at concentrations ranging from 5 X 10(2) to 10(5) U/L; 10(5) U/L of IL-1 suppressed DNA synthesis by more than 40% of control. The suppressive activity of IL-1-beta was more potent than that of IL-1-alpha in spite of the same lymphocytes activating factor (LAF) activity. Steady state levels of c-myc mRNA transcripts were also inhibited by both IL-1-alpha and beta, respectively. On the other hand, IL-1-alpha and beta did not affect the WRO cell growth. Although forskolin stimulated cAMP production in NPA cells, IL-I did not induce cAMP generation. Indomethacin (1.0 approximately 10 mg/L) did not alter the suppressive activity of IL-1. Neither IL-1-alpha and beta caused a cytotoxic effect on the NPA cells. Although changes in c-myc mRNA content may just be an epiphenomenon of the decrease in proliferative activity in response to IL-1, and not a direct target of action of the peptide, these results demonstrate the inhibitory effect of IL-1 on cell growth of NPA. IL-1 may have an aspect of antitumorigenic action in some human thyroid carcinoma differentiation and replication.