The effect of particle wear debris on NFκB activation and pro-inflammatory cytokine release in differentiated THP-1 cells

Orthopedic wear debris has been thought to be an important factor associated with osteolysis and loosening of total joint arthroplasties. Previous in vitro studies have reported that particles of wear debris induce the release of pro-inflammatory cytokines and other inflammatory mediators from macrophages and other cells. Several recent investigations, however, have suggested that the wear particles themselves may not be primarily responsible for the inflammatory cellular responses, but that the observed cytokine release in vitro may be caused by endotoxin adsorbed to commercially available particle preparations. The intracellular pathways involved in macrophage signal transduction also are poorly understood. The purposes of this study are to use isolated orthopedic wear debris particles to evaluate pro-inflammatory cytokine release and nuclear factor kappa B (NF kappaB) activation from macrophages. Cells from human monocyte/macrophage cell line (THP-1) were differentiated and incubated with particles of debris that had been isolated from a failed human total hip arthroplasty. The titanium-alloy particles did not evoke release of TNF-alpha or IL-1 beta whereas lipopolysaccharide (LPS) or LPS-treated debris particles induced both TNF-alpha and IL-1 beta. LPS-treated particles, but not particles alone, stimulated NF kappaB activation. Our results suggest that at the concentrations tested in this study, endotoxin-free wear debris particles may not themselves initiate inflammatory cellular responses in differentiated THP-1 cells. It is unclear whether adsorbed endotoxin is clinically associated with osteolysis and/or loosening in total joint arthroplasties, but several factors, including adsorbed endotoxin, need to be investigated to explore the cellular responses responsible for osteolysis and/or loosening. (C) 2001 John Wiley & Sons, Inc. J Biomed Mater Res 59: 507-515,2002.