Preferential inhibition of cytokine-stimulated bone resorption by recombinant interferon gamma.

It is likely that immune cells in the bone marrow produce factors which are involved in the local control of bone remodeling. Immune cell products such as interleukin-1 and the tumor necrosis factors are potent stimulators of bone resorption in vitro. In this paper, we have studied the effects of recombinant murine interferon-gamma on bone resorption stimulated by these agents and the systemic calcium-regulating hormones 1,25(OH)2 vitamin D3 and parathyroid hormone. We found that interferon-gamma completely abolished bone resorption stimulated by the cytokines interleukin-1, tumor necrosis factor alpha and tumor necrosis factor beta. In contrast, parathyroid hormone- and 1,25(OH)2 vitamin D3-stimulated bone resorption were not significantly affected by the addition of interferon-gamma under the same conditions. Parathyroid hormone-stimulated bone resorption was inhibited slightly when larger concentrations of interferon-gamma were used for more prolonged periods. The inhibitory effects on cytokine-stimulated bone resorption occurred at interferon concentrations of 100 U/ml (half-maximal) to 300 U/ml (complete inhibition). This relatively selective inhibition of cytokine-stimulated bone resorption by an immune cell product may have physiological significance in the local control of trabecular bone volume and bone remodeling.