Comparison of the response of primary human peripheral blood mononuclear phagocytes from different donors to challenge with model polyethylene particles of known size and dose

The response of primary human peripheral blood mononuclear phagocytes to ch allenge with polyethylene particles of known size and dose was evaluated. P articles with mean sizes of 0.21, 0.49, 4.3, 7.2, and 88 mu m were co-cultu red with cells for 24 h prior to the assessment of cell viability and produ ction of the osteolytic mediators IL-1 beta, IL-6, TNF alpha, GM-CSF and PG E(2). All particle fractions were evaluated at particle volume (mu m(3)) to cell number ratios of 10: 1 and 100: 1 which were previously identified as being the most biologically active and clinically relevant. The heterogene ity of human individuals was clearly evident both in the profile and the ma gnitude of the response of the donors evaluated in this study (the response of donor 5 being 2- to 15-fold lower than that of the other donors). Only the sub-micrometre particles stimulated significantly enhanced cytokine sec retion at the ratios tested: mean particle sizes of 0.49 and 0.21 mu m bein g the most biologically active. Macrophages stimulated with particles outsi de this size range produced considerably lower levels of mediator. These re sults compared favourably with the results of earlier studies, which demons trated that particles within the phagocytosable size range (0.1-10 mu m) we re the most biologically active. These results, therefore, confirm earlier findings and suggest that the size and volume of polyethylene particles are critical factors in macrophage activation. Furthermore, they suggest that the heterogeneity of human individuals may be another important factor in d etermining implant life and could provide the basis for a valuable diagnost ic tool to identify those patients most at risk of implant loosening. (C) 2 000 Elsevier Science Ltd. All rights reserved.