1-Hydroxyethylidene-1,1-bisphosphonate decreases the postovariectomy enhanced interleukin 1 secretion from peritoneal macrophages in adult rats.

Abstract

Bisphosphonates are potent inhibitors of bone resorption. In previous studies, we have shown that ovariectomy accelerates bone resorption and 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) inhibits ovariectomy-accelerated bone resorption in female Wistar adult rats. As interleukin 1 (IL-1) stimulates bone resorption in vitro and in vivo, we have investigated the effects of ovariectomy and HEBP administered in vivo on IL-1 secretion from peritoneal macrophages in adult rats. Ovariectomy or sham surgery were performed in female Wistar rats at 40 weeks of age. Ovariectomized and sham-operated rats were administered with HEBP (10 mg) or saline, 10 times in total, from 43 to 46 weeks of age. Paraffin oil-induced peritoneal macrophages at 46 weeks of age were cultured for 24 hours. Lipopolysaccharide (LPS)-stimulated peritoneal macrophages from ovariectomized rats secreted more IL-1 than sham-operated rats. HEBP decreased LPS-stimulated IL-1 secretion from peritoneal macrophages in ovariectomized rats, but not in sham-operated rats. In vivo administration of HEBP decreased IL-1 secretion only in postovariectomy hyperresorptive states. These results suggest that alterations in LPS-stimulated IL-1 secretion from oil-induced peritoneal macrophages may be responsible, at least in part, for the postovariectomy acceleration in bone resorption and its inhibition by HEBP.