The effect of interleukin-6 and soluble interleukin-6 receptor protein on the bone resorptive activity of human osteoclasts generated in vitro.

The role of interleukin-6 (IL-6) in the regulation of bone resorption is controversial and has not been studied using human tissue in vitro. This study exploits a recently described in vitro model, whereby osteoclasts, defined as cells that resorb bone, can be generated from human bone marrow, and investigated the effect of IL-6 and its soluble receptor on bone resorption, in the presence of 1,25-dihydroxyvitamin D3 [1,25(OH)2 vitamin D3]. Human bone marrow was cultured to form a confluent stroma, sedimented onto devitalized bone slices, and recharged with non-adherent bone marrow cells. 1,25(OH)2 vitamin D3 increased bone resorption, whereas IL-6 failed to induce a similar stimulatory effect. Both IL-6 at 100 ng/ml and soluble IL-6 receptor protein in the absence of exogenous IL-6 inhibited the stimulatory effect of 1,25(OH)2 vitamin D3. Bone resorption was never observed when non-adherent haemopoietic cells were cultured in the absence of stroma but in the presence of IL-6, which indicates that IL-6 cannot replace the stromal factor(s) required for the formation of cells capable of resorbing bone. These results suggest that IL-6 at high concentrations is not a critical cytokine in stimulating osteoclastic bone resorption.