Human macrophage response to UHMWPE, TiAlV, CoCr, and alumina particles: analysis of multiple cytokines using protein...

Aseptic loosening of total joint replacements is believed to be initiated by a macrophage response to prosthetic wear debris. To better characterize the early response to clinically relevant wear debris, we challenged primary human macrophages from four donors with ultra high molecular weight polyethylene (UHMWPE), TiAlV, CoCr, and alumina particles. After a 24-h culture, protein arrays were used to quantify the secretion of 30 different cytokines and chemokines. Macrophages secreted detectable levels of nine mediators in culture: Interleukin-1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), IL-1beta, MCP-1, IL-8, IL-6, GM-CSF, IL-10, and IL-12p40. TiAlV particles were the most stimulatory, causing 5- to 900-fold higher cytokine expression compared with nonstimulated cells and uniquely eliciting high levels of IL-1alpha, IL-6, IL-10, and GM-CSF. CoCr and alumina were mildly stimulatory and typically elicited two- to fivefold greater levels than nonstimulated cells. Surprisingly, UHMWPE did not elicit a significant increase in cytokine release. Our data suggests that IL-1alpha, TNF-alpha, IL-1beta, and MCP-1 are the primary initiators of osteolysis and implicates metallic debris as an important trigger for their release.