Triiodothyronine potentiates the stimulatory effects of interleukin‐1β on bone resorption and medium interleukin‐6 content in fetal rat limb bone cultures

It has been demonstrated that thyroid hormones stimulate osteoclasts indirectly and that this effect is mediated by products of other cell types 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 (T₃) on bone resorption (⁴⁵Ca release) and on the IL‐6 concentration in medium from cultured 19‐day‐old fetal rat limb bones. T₃ alone increased ⁴⁵Ca release significantly only at a fairly high concentration (10⁻⁶ M) under the conditions used. T₃ alone, over a 10⁻¹¹–10⁻⁶ M concentration range, failed to elicit a detectable effect on the medium IL‐6 content. However, T₃ potentiated the stimulatory effect of interleukin‐1β (IL‐1β) on IL‐6 production in a dose‐dependent manner. T₃, 10⁻⁸ M, also significantly increased IL‐1β‐stimulated calcium release. Inhibition of IL‐1β with 1 μM interleukin‐1 receptor antagonist (IL‐Ira) abrogated the potentiating effects of T₃ on IL‐1β‐stimulated IL‐6 production and blocked the combined effect of T₃ and IL‐1β on ⁴⁵Ca release. One micromolar indomethacin significantly, but not completely, inhibited the effect of IL‐1β, as well as the combined effect of IL‐1β and T₃ on resorption and IL‐6 production, indicating the involvement of prostaglandins in these actions. Consistent with this, 1 μM prostaglandin E₁ (PGE₁) significantly increased both the IL‐6 production and the calcium release. By potentiating the effect of IL‐1β, T₃ increased bone resorption at much lower concentrations. We therefore speculate that the enhancement of IL‐1β effects may be a biologically relevant mechanism of thyroid hormone action on bone.