Experimental heterotopic bone formation induced by bone morphogenetic protein and recombinant human interleukin-1B

The object of this research is to investigate the influence of interleukin-1 (IL-1) on heterotopic ossification (HO) induced by bone morphogenetic protein (BMP). Adult mice were implanted with doses of 1, 2, 5, and 10 mg of BMP. Several local injections of 10, 100, and 1000 units of a recombinant IL-1 beta (rIL-1 beta) were administered during the morphogenetic phase of development, starting a day before operation until one week postoperation. While IL-1 acts principally on cell proliferation, BMP primarily shows cell differentiation in the form of HO. BMP-induced HO is quantitated by computer X-ray image scanning, bone ash weight, alkaline phosphatase activity, and histological methods. The area of human BMP-induced HO was completely abolished by injections of polyclonal and monoclonal anti-IL-1 antibody. Monoclonal antibody did not cross-react with the same efficiency as polyclonal with bovine BMP. Polyclonal anti-IL-1 antibody totally neutralizes bovine BMP activity. IL-1-enhanced BMP induced HO and increased the volume of new bone in a statistically significant increment.