Prolonged and ubiquitous inhibition by interferon gamma of bone resorption induced by parathyroid hormone-related protein, 1,25-dihydroxyvitamin D3, and interleukin 1 in fetal mouse forearm bones.
To investigate the mechanism of the inhibitory effects of interferon-gamma (IFN-gamma) on bone resorption, the effects of murine IFN-gamma on 45Ca release from prelabeled fetal mouse forearm bones were investigated. Murine IFN-gamma usually did not affect basal 45Ca 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-1 alpha 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 and 45Ca release from the IFN-gamma-treated forearm bones. The inhibitory effect of IFN-gamma on bone resorption induced by PTH-rP (1-34) or IL-1 alpha continued during 6 days of culture, whereas that of calcitonin disappeared after 2 days of culture. These findings suggest that IFN-gamma non-preferentially 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-gamma-treated bones, the cytokine may be potentially useful for treatment of certain patients with malignancy-associated hypercalcemia.
Fujii
Y
Y
Institute of the Foundation for Growth Science, Tokyo, Japan.
Sato
K
K
Kasono
K
K
Satoh
T
T
Fujii
T
T
Shizume
K
K
D000818:Animals; D001862:Bone Resorption / Q000139:chemically induced*; D001842:Bone and Bones / Q000187:drug effects* / Q000502:physiology; D002116:Calcitonin / Q000494:pharmacology; D002117:Calcitriol / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005542:Forearm; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D010281:Parathyroid Hormone / Q000494:pharmacology; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000494:pharmacology; D011247:Pregnancy; D011506:Proteins / Q000494:pharmacology*; D019379:Teriparatide
D007375:Interleukin-1; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D019379:Teriparatide; C054296:parathyroid hormone-related protein (1-34); D007371:Interferon-gamma; D002116:Calcitonin; D002117:Calcitriol; D015232:Dinoprostone