Inhibition of polymethylmethacrylate particle-induced monocyte activation and IL-1β and TNF-α expression by the antioxidant agent N-acetylcysteine

Abstract

We investigated the effectiveness of an antioxidant agent, N-acetylcysteine (NAC), in suppressing macrophage activation and mediator release in response to particulate debris. Polymethylmethacrylate (PMMA) particle-stimulated monocyte-macrophages were cultured alone and with varying concentrations of NAC. Tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β) expression in the resultant cultures were measured using enzyme-linked immunosorbant assays. The ultrastructural effect of treatment was also assessed by electron microscopy. Cell viability in the various cultures was measured to rule out an effect of cytotoxicity. NAC treatment reduced TNFα and IL-1β expression by the monocyte-macrophages. Culturing with NAC was also associated with less ultrastructural activation of the monocytes. Furthermore, NAC was not associated with any adverse effect on cell viability in the concentrations used. Our findings demonstrate the effectiveness of the antioxidant N-acetylcysteine in suppressing the cell activation and TNF-α release seen on exposure to wear debris. This represents a novel potential therapeutic method in the prevention or treatment of periprosthetic osteolysis.