Inhibition of polymethylmethacrylate particle-induced monocyte activation and IL-1beta and TNF-alpha expression by the antioxidant agent N-acetylcysteine.
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 alpha (TNFalpha) and interleukin-1beta (IL-1beta) 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 TNFalpha and IL-1beta 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 TNFalpha release seen on exposure to wear debris. This represents a novel potential therapeutic method in the prevention or treatment of periprosthetic osteolysis.
Mulhall
Kevin J
KJ
Department of Orthopaedics, Merlin Park Hospital, Galway, Ireland. kjm@indigo.ie
Curtin
William A
WA
Given
H Frederick
HF
D000111:Acetylcysteine / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors*; D001843:Bone Cements / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D053583:Interleukin-1beta; D008222:Lymphokines / Q000037:antagonists & inhibitors* / Q000187:drug effects* / Q000648:ultrastructure; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D009000:Monocytes / Q000187:drug effects*; D010316:Particle Size; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000187:drug effects*; D019904:Polymethyl Methacrylate / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000187:drug effects*
D000970:Antineoplastic Agents; D001843:Bone Cements; D016166:Free Radical Scavengers; D007375:Interleukin-1; D053583:Interleukin-1beta; D008222:Lymphokines; D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C052994:interleukin-1beta (163-171); D019904:Polymethyl Methacrylate; D000111:Acetylcysteine