Signaling Pathways for Tumor Necrosis Factor-α and Interleukin-6 Expression in Human Macrophages Exposed to Titanium-Alloy Particulate Debris in Vitro*

Background: Loosening of the implant after total joint arthroplasty remains a serious problem. The acti-vation of macrophages by wear debris from implants, mediated by the release of cytokines that elicit bone resorption, may lead to loosening. The purpose of the present study was to elucidate the mechanisms of macrophage activation by titanium particles from the components of implants and to identify the signal-ing pathways involved in particle-mediated release of cytokines. Methods: Macrophages were isolated from mono-nuclear leukocytes obtained from healthy human do-nors and were exposed to titanium-alloy particles that had been obtained from periprosthetic membranes col