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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\u2010h 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\u20101\u03b1 (IL\u20101\u03b1), tumor necrosis factor\u2010\u03b1 (TNF\u2010\u03b1), IL\u20101\u03b2, MCP\u20101, IL\u20108, IL\u20106, GM\u2010CSF, IL\u201010, and IL\u201012p40. TiAlV particles were the most stimulatory, causing 5\u2010 to 900\u2010fold higher cytokine expression compared with nonstimulated cells and uniquely eliciting high levels of IL\u20101\u03b1, IL\u20106, IL\u201010, and GM\u2010CSF. CoCr and alumina were mildly stimulatory and typically elicited two\u2010 to fivefold greater levels than nonstimulated cells. Surprisingly, UHMWPE did not elicit a significant increase in cytokine release. Our data suggests that IL\u20101\u03b1, TNF\u2010\u03b1, IL\u20101\u03b2, and MCP\u20101 are the primary initiators of osteolysis and implicates metallic debris as an important trigger for their release. \u00a9 2007 Wiley Periodicals, Inc. 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