Prolonged and ubiquitous inhibition by interferon γ of bone resorption induced by parathyroid hormone-related protein, 1,25-dihydroxyvitamin D3, and interleukin 1 in fetal mouse forearm bones

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Abstract
To investigate the mechanism of the inhibitory effects of interferon-γ (IFN-γ) on bone resorption, the effects of murine IFN-γ on45Ca release from prelabeled fetal mouse forearm bones were investigated. Murine IFN-γ usually did not affect basal45Ca release but almost completely and equipotently inhibited bone resorption induced by PTH(1-34), PTH-rP(1-34), 1,25(OH)2D3, and interleukin 1 (IL-1). The half-maximal concentration for inhibition of bone resorption induced by IL-1α was 25.8±14.6 U/ml (mean±SD for 13 experiments), which is not different from those for PTH, PTH-rP, and 1,25(OH)2D3. There was no correlation between prostaglandin E2 concentration in the conditioned medium and45Ca release from the IFN-γ-treated forearm bones. The inhibitory effect of IFN-γ on bone resorption induced by PTH-rP (1-34) or IL-1α continued during 6 days of culture, whereas that of calcitonin disappeared after 2 days of culture. These findings suggest that IFN-γ nonpreferentially inhibits bone resorption induced by various bone-resorbing factors in fetal mouse forearm bones via a PGE2-independent mechanism. As no escape phenomenon developed in IFN-γ-treated bones, the cytokine may be potentially useful for treatment of certain patients with malignancy-associated hypercalcemia.

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