INTERLEUKIN-1 STIMULATES THYROID CELL GROWTH AND INCREASES THE CONCENTRATION OF THE c-myc PROTO-ONCOGENE mRNA IN THYROID FOLLICULAR CELLS IN CULTURE

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Abstract
In the course of studies of cell-mediated immunity in Graves'' disease, we noted that normal peripheral blood monocytes, when stimulated by bacterial lipopolysaccharide, conditioned their media with a factor that had the physicochemical properties of the lymphokine interleukin-1 (IL-1) and that enhanced DNA synthesis and replication in quiescent FRTL5 cells, a line of nontransformed rat thyroid follicular cells. This finding led to the present studies, in which the effect of IL-1 (recombinant IL-1-.beta.) on DNA synthesis in FRTL5 was explored. In the absence of serum, IL-1 induced a small, but significant, increase in [3H]thymidine incorporation into DNA. Calf serum (0.5%) alone also stimulated DNA synthesis slightly, but it greatly enhanced, in asynergistic manner, the stimulatory response to IL-1, decreasing the minimally effective concentrations of IL-1 and amplifying the response to higher concentrations. A similar synergism was noted when quiescent FRTL5 were cultured with a combination of IL-1 and a low concentration of insulin-like growth factor-I (IGF-I), which itself stimulated DNA synthesis modestly. IL-1 also increased levels of the mRNA of the proto-oncogene c-myc in findings indicate that IL-1 is an independent stimulator of thyroid cell growth, and that its effects are greatly enhanced by serum, probably in large measure by the IGF-1 contained therein. They raise the possibility that IL-1 generated locally by intrathyroid macrophages may act directly by a short-loop mechanism to increase goiter formation in autoimmune thyroid disease.