Chronic intramedullary infusion of interleukin-1 alpha increases bone mineral content in rats.

Interleukin-1 (IL-1) is known to have a potent bone-resorbing activity in vitro, however, results from in vivo studies are conflicting. We performed experiments with the continuous infusion of recombinant IL-1 alpha directly into the femoral bone marrow of rats for 2 weeks and examined its effects on bone by soft X-ray photographs, bone mineral assessment, and histological examination. Infusion of IL-1 alpha at doses greater than 1 microgram/ml (0.6 ng/hour) caused sclerosis around the infusion site on soft X-ray photographs, and the bone mineral content of IL-1 alpha infused femora was increased significantly. Histologically, extensive periosteal bone formation was observed around the infusion site and small mononuclear cells replaced the normal fat tissue. Infusion of prostaglandin E2 alone produced intramedullary bone formation more extensively. Simultaneous infusion of IL-1 alpha and indomethacin (10(-3) M; 179 ng/hour) inhibited the increase of bone mineral content (BMC) induced by IL-1 alpha. Thus, the chronic intramedullary administration of IL-1 alpha stimulates bone formation, especially in the periosteum, and increases BMC in intact rats.