Synergistic effects of mixed TiAlV and polyethylene wear particles on TNFalpha response in THP-1 macrophages.

TNFalpha is a potent osteoclastogenic cytokine that has a fundamental role in the pathogenesis of wear particle-induced osteolysis. Wear particles of one composition and their biological effects are well characterised. In contrast, little is known about the effects of mixed particles with respect to mix ratio and particle concentration. We evaluated the effects of different mix ratios of polyethylene and TiAlV particles on TNFalpha response. We used a human monocytic cell line (THP-1) in this in vitro study. THP-1 monocytes were differentiated to macrophage-like cells and exposed to different mixtures of lipopolysaccharide-detoxified polyethylene and TiAlV particles. TNFalpha was analysed in culture supernatants using ELISAs. Both polyethylene and TiAlV particles induced a dose- and time-related release of TNFalpha, with maximum levels after 6 h. A PE/TiAlV mix ratio of 36:1 at 10(8) particles/ml induced significantly higher TNFalpha concentrations compared to equal particle concentrations of isolated TiAlV (p=0.047) or PE (p=0.044), indicating the synergistic effect of mixed particles. These results provide evidence that TiAlV and polyethylene particles have significant synergistic effects, depending on the mix ratio and particle concentrations. This supra-additive effect can contribute substantially to the pathogenesis of implant particle-induced osteolysis.