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

TNF alpha is a potent osteoclastogenic cytokine that has a fundamental role in the pathogenesis of wear particleinduced 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 TiAIV particles on TNF alpha 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 TiAIV particles. TNF alpha was analysed in culture supernatants using ELI-SAs. Both polyethylene and TiAIV particles induced a dose- and time-related release of TNIF alpha, with maximum levels after 6 h. A PE/TiAIV mix ratio of 36:1 at 10(8) particles/ml induced significantly higher TNFa. concentrations compared to equal particle concentrations of isolated TiAIV (p = 0.047) or PE (p = 0.044), indicating the synergistic effect of mixed particles. These results provide evidence that TiAIV 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.