Polyethylene particles of a ‘critical size’ are necessary for the induction of cytokines by macrophages in vitro

Particulate wear debris from total hip prosthetic components can stimulate macrophages to produce mediators of osteolysis which may cause aseptic implant loosening. This study evaluated the in vitro response of murine peritoneal macrophages to polyethylene particles of difinitive size distributions at varying volume doses. Ceridust 3615 polyethylene particles with a mean size of 0.21, 0.49, 4.3 and 7.2 μm and GUR1120 polyethylene resin with a mean size of 88 μm were co-cultured with C3H murine peritoneal macrophages at volume (μm) 3 to cell number ratios of 100 : 1, 10 : 1, 1 : 1 and 0.1 : 1. The secretion of IL-6, IL-1 β and TNF- α was determined by ELISA. Significantly elevated levels of TNF- α and IL-1 β were determined at 100 : 1 ratios when the macrophages were challenged with particles with a mean size of 0.49, 4.3 and 7.2 μm, and at 10 : 1 ratios for particles with a mean size of 0.49 and 4.3 μm. IL-6 production was significantly elevated at 100 : 1 ratios for mean particle sizes of 0.49 and 4.3 μm. Particles outside this range produced considerably less cytokine suggesting that both the size and volume (or number) of polyethylene particles are critical factors in macrophage activation. Therefore particles in the phagocytosable size range of 0.3–10 μm appear to be the most biologically active.