MECHANISMS OF CELLULAR RECRUITMENT IN ASEPTIC LOOSENING OF PROSTHETICJOINT IMPLANTS

The association of macrophages engaged in polymethylmethacrylate (PMMA ) particle phagocytosis with pockets of inflammatory cells is a pathog nomonic feature of the aseptically loose interface not present at the well-fixed interface. The mechanism by which the presence of PMMA part icles leads to cellular recruitment, bone resorption, and ultimate loo sening is poorly understood. Granulocyte macrophage colony stimulating factor (GM-CSF) and interleukin 6 (IL-6), cytokines released by osteo blasts, stimulate the recruitment of macrophages into sites of inflamm ation. We show that exposure of macrophages to PMMA particles stimulat ed release of tumor necrosis factor (TNF), but no increase in prostagl andin E2 (PGE-2) or interleukin 1. Incubation of osteoblasts with cond itioned medium from macrophages exposed to PMMA particles led to relea se of GMCSF, IL-6, and PGE-2. Incubation of the PMMA/macrophage medium with antibodies to TNF prior to osteoblast exposure inhibited release of GM-CSF, IL-6, and PGE-2 by the osteoblasts. Our data demonstrate t hat exposure of macrophages to PMMA particles leads to the release of TNF which then stimulates osteoblasts to produce GM-CSF, IL-6, and PGE -2. Based upon the results of this study, we propose that the process of cellular recruitment in aseptic loosening is initiated when the mec hanical failure of the cement mantle leads to the production of PMMA p articles. These particles are phagocytized by macrophages leading to t he production of TNF. TNF stimulates surrounding osteoblasts to produc e GM-CSF, IL-6, and PGE-2 which leads to recruitment of macrophages an d osteoclasts into the area of the bone-cement interface. The recruitm ent of these cells potentiates this process leading to bone resorption and ultimately, clinical loosening of prosthetic joint implants.