Interleukin-1β Modulates Thyrotropin-Induced Thyroglobulin mRNA Transcription through 3′,5′-Cyclic Adenosine Monophosphate*

It has been reported that interleukin-1 possesses not only immunoregulatory action, but also multiple hormone like effects. We studied the action of recombinant interleukin-1 beta (IL-1 beta) on the synthesis of thyroglobulin (TG), the precursor of thyroid hormone. Human thyrocytes dispersed from normal and Graves' thyroid tissues were incubated with TSH with or without IL-1 beta. TSH stimulated TG release from cultured human thyrocytes after 4 days. This effect was mimicked by dibutyryl cAMP (dBcAMP). IL-1 beta had no effect on basal TG release but modulates the TSH-stimulated TG secretion. At low dose (10(-5) to 10(-3) U/ml) IL-1 beta increased the TSH-stimulated TG secretion while higher doses (1-100 U/ml) of IL-1 beta had an inhibitory effect. Similar responses were observed with both normal and Graves' thyrocytes. The effect of IL-1 beta occurred at the gene transcription level as reflected by changes in TG mRNA level. At 100 U/ml, IL-1 beta suppressed TG mRNA level to near unmeasurable level. This biphasic effect of IL-1 beta on TG synthesis is paralleled by a similar change in TSH-stimulated cAMP secretion. We conclude that IL-1 beta possesses hormonal action on TG gene transcription and its effect is mediated via cAMP.