INTERFERON-GAMMA CAUSES LOSS OF BONE VOLUME IN-VIVO AND FAILS TO AMELIORATE CYCLOSPORINE-A-INDUCED OSTEOPENIA

Interferon-gamma (IFN gamma) in vitro inhibits both bone resorption an d bone formation, resulting in a net decrease in bone turnover. In viv o administration of cyclosporin A (CsA) produces accelerated bone remo deling with resultant bone loss. The aim of this study was to investig ate whether administration of IFN gamma to rats would favorably modify the high turnover osteopenia caused by CsA. Thirty-six male Sprague-D awley rats were randomized into 4 equal groups to receive either CsA ( 15 mg/kg.day) or vehicle by gavage and IFN gamma (10(6) IU/kg.day) or vehicle by ip injection for 8 days. Group 1 received CsA vehicle plus IFN gamma vehicle; group 2 received CsA plus IFN gamma vehicle; group 3 received CsA vehicle plus IFN-gamma; group 4 received CsA plus IFN g amma. Blood was sampled on days 0, 4, and 8 for measurement of ionized calcium (Ca2+), PTH, 1,25-dihydroxyvitamin D, and bone gla protein. T ibiae were removed on day 8 after double tetracycline labeling for his tomorphometric analysis. Ca2+ and PTH levels were similar in all group s during the study period. Rats receiving CsA (groups 2 and 4) had ele vated levels of 1,25-dihydroxyvitamin D and bone gla protein, whereas rats receiving IFN gamma alone (group 3) had no change in levels of th ese parameters. Bone histomorphometry revealed that treatment with CsA and/or IFN gamma (groups 2-4) caused an increase in bone resorption s urface and a decrease in some parameters of bone formation, resulting in a net loss of bone volume. Thus, IFN gamma failed to influence the osteopenia caused by CsA and on its own had adverse effects on bone in vivo. These results demonstrate that immune-mediating agents have opp osing actions in vitro as compared to in vivo.