Evaluation of the response of primary human peripheral blood mononuclear phagocytes to challenge with In vitro generated clinically relevant UHMWPE particles of known size and dose

The response of primary human peripheral blood mononuclear phagocytes to ch allenge with clinically relevant ultra-high molecular weight polyethylene ( UHMWPE) wear debris of known particle size and dose was evaluated. Particle s with a mean size of 0.24, 0.45, 1.7, 7.6, and 88 mu m were cocultured wit h cells for 24 h before assessment of cell viability and production of the osteolytic cytokines interleukin (IL)-1 beta, IL-6, tumor necrosis factor-a lpha, and granulocyte macrophage colony-stimulating factor, and prostagland in E-2. All particle fractions were evaluated at particle volume (mu m(3)) to cell number ratios of 10:1 and 100:1, which had been previously identifi ed as being the most stimulatory and clinically relevant. None of the test fractions had an effect on cell viability. Whereas the heterogeneity of hum an individuals was clearly evident in the responses of the donors evaluated in this study (the response of donor 3 was between 5 and 20 times greater than the other donors), the most biologically active particles were found t o be submicrometer in size. Stimulation with phagocytosable particles (0.24 , 0.45, and 1.7 mu m) resulted in enhanced levels of cytokine secretion. Ma crophages stimulated with particles outside this size range produced consid erably less cytokines at the volumes tested. These results confirm earlier findings and suggest that the size and volume of UHMWPE particles are criti cal factors in macrophage activation. Furthermore, they suggest that the he terogeneity of human individuals may he another important factor in determi ning implant life. (C) 2000 John Wiley & Sons, Inc.