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

Abstract

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 interferonγ 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-7 completely abolished bone resorption stimulated by the cytokines interleukin-1, tumor necrosis factor α and tumor necrosis factor ß. In contrast, parathyroid hormone- and 1,25(OH)₂ vitamin D₃-stimulated bone resorption were not significantly affected by the addition of interferon-γ under the same conditions. Parathyroid hormone-stimulated bone resorption was inhibited slightly when larger concentrations of interferon-γ 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.