TRIIODOTHYRONINE POTENTIATES THE STIMULATORY EFFECTS OF INTERLEUKIN-1-BETA ON BONE-RESORPTION AND MEDIUM INTERLEUKIN-6 CONTENT IN FETAL-RATLIMB BONE CULTURES

It has been demonstrated that thyroid hormones stimulate osteoclasts i ndirectly and that this effect is mediated by products of other cell t ypes present in bone. To determine if interleukin-6 (IL-6) could be a mediator of thyroid hormone action, we investigated the effect of 3,5, 3'-triiodothyronine (T-3) on bone resorption (Ca-45 release) and on th e IL-6 concentration in medium from cultured 19-day-old fetal rat limb bones. T-3 alone increased Ca-45 release significantly only at a fair ly high concentration (10(-6) M) under the conditions used. T, alone, over a 10(-11)-10(-6) M concentration range, failed to elicit a detect able effect on the medium IL-6 content. However, T-3 potentiated the s timulatory effect of interleukin-1 beta (IL-1 beta) on IL-6 production in a dose-dependent manner. T-3, 10(-8) M, also significantly increas ed IL-1 beta-stimulated calcium release. Inhibition of IL-1 beta with 1 mu M interleukin-1 receptor antagonist (IL-1ra) abrogated the potent iating effects of T-3 on IL-1 beta-stimulated IL-6 production and bloc ked the combined effect of T-3 and IL-1 beta on Ca-45 release. One mic romolar indomethacin significantly, but not completely, inhibited the effect of lL-1 beta, as well as the combined effect of IL-1 beta and T , on resorption and IL-6 production, indicating the involvement of pro staglandins in these actions. Consistent with this, 1 mu M prostagland in E(1) (PGE(1)) significantly increased both the IL-6 production and the calcium release. By potentiating the effect of IL-1 beta, T, incre ased bone resorption at much lower concentrations. We therefore specul ate that the enhancement of IL-1 beta effects may be a biologically re levant mechanism of thyroid hormone action on bone.