Effect of bisphosphonates on production of interleukin 1-like activity by macrophages and its effect on rabbit...

Bisphosphonates are potent inhibitors of bone resorption, but their mode of action is still unknown. Since interleukin 1 (IL-1)-like activity has been shown to stimulate bone resorption in vitro, we have studied whether bisphosphonates inhibit either the production of IL-1-like activity or its effect on one type of connective tissue cell, chondrocytes. The production of IL-1-like activity was examined using rabbit peritoneal macrophages and the murine macrophage cell line P388D1, and the effect of IL-1-like activity was assessed by measuring the secretion of collagenase and prostaglandin E2 (PGE2) by rabbit chondrocytes. Production of IL-1-like activity was unaffected by bisphosphonates, whereas the effect of IL-1-like activity on collagenase and prostaglandin E2 secretion by rabbit chondrocytes was increased rather than inhibited by bisphosphonates. Finally, bisphosphonates increased DNA and cell number in chondrocyte cultures, but this effect was blocked when IL-1-like activity was added to the cultures. Thus, our results provide no evidence for a direct inhibitory effect of bisphosphonates on either the production of IL-1-like activity or the action of IL-1-like activity on chondrocytes.