OSTEOCLASTS AND EFFECTS OF INTERLEUKIN-4 IN DEVELOPMENT OF CHRONIC OSTEOMYELITIS

The cellular response to trauma and infection was studied in a murine model of posttraumatic osteomyelitis. Osteoclast response differed mar kedly depending on whether infection with Staphylococcus aureus accomp anied the bone trauma. In animals recovering from sterile trauma, oste oclastic activity that was limited to the damaged or dead bone fragmen ts caused rapid elimination of all recognizable dead bone within 1 wee k, New bone was laid down in an orderly fashion. Animals with superimp osed infection had an intense polymorphonuclear leukocyte response dev elop. Additionally, osteoclasts behaved as acute inflammatory responde rs with substantial activity at the margins of the infected site and a t previously uninjured tibial cortex adjacent to the infection. Despit e the exuberant osteoclast response, bony fragments were not resorbed (for at least 4 weeks after the trauma), that is, sequestra developed, and new bone was laid down over morphologically dead bone and on the cortex (involucrum). When the inhibitory cytokine, interleukin 4 was g iven in a single dose with the bacterial inoculum, the osteoclast resp onse was moderated with almost complete elimination of osteoclast acti vity at normal tibial cortex adjacent to the infected site. The limita tion of osteoclastic activity did not impair the host's containment of bacterial growth.