Evaluation of endotoxin binding to uhmwpe and inflammatory mediator production by macrophages

The purpose of this investigation was 1) to determine if endotoxin can bind to the surface of high molecular weight polyethylene (UHMWP) implants in concentrations that elicit an inflammatory response, and 2) to determine if endotoxin differentially adheres to polyethylene surfaces of either oxidized ("aged") or unoxidized ("new"). Endotoxins are a major constituent of gram-negative bacteria and can stimulate the release of inflammatory mediators (e.g. IL-1) and nitric oxide (NO). Activation of IL-1 can stimulate osteolysis, therefore contributing to implant failure. Results suggest that a dose as low as 1microg/mL endotoxin was enough to elicit an inflammatory response in macrophage cell cultures without hindering cellular viability. Levels of NO were elevated in all groups treated with 1 microg/mL, 2 microg/mL, and 10 microg/mL of endotoxin, however, dose dependence was not observed. Similar findings were detected for cytokine levels of IL-1. Studies have shown wear particle debris can result in increased levels of IL-1 and NO, which lead to osteolysis. Our findings suggest that endotoxin can bind both "aged" and "new" UHMWP in a similar manner. Endotoxin also causes increases in IL-1 and NO, which lead to osteolysis. Additional studies are needed to determine if phagocytosis of wear particles can significantly increase NO and lead to osteolysis.