Effect of anti-inflammatory medication on monocyte response to titanium particles

Cytokines produced by macrophages in the periprosthetic membranes surroundi ng joint replacements have been implicated as causal agents in osteolysis a nd prosthetic loosening. The present study characterizes the response of hu man peripheral blood monocytes to titanium particles. Monocytes were obtain ed from donated blood and were cultured in the presence of different-sized titanium particles. Exposure to tiranium-aluminum-vanadium particles signif icantly changed the release of tumor necrosis factor-alpha (TNF-alpha), int erleukin-6 (IL-6), and interleukin-1 (IL-1), whereas there was no significa nt effect on the release of prostaglandin E-2 (PGE(2)). When monocytes were cultured with par ticles, the titanium alloy particles induced significant ly more release of TNF-alpha and less IL-1 secretion. Ciprofloxacin inhibit ed production of TNF-alpha, IL-6, IL-1, and PGE(2) in human monocytes expos ed to titanium particles. In contrast to ciprofloxacin, indomethacin was no t a potent inhibitor of TNF-alpha production but potentiated IL-6 productio n in titanium-stimulated monocytes. Indomethacin had no effect on the produ ction of IL-1 and was a potent inhibitor of PGE(2) production in titanium-s timulated monocytes. Pentoxifylline had an inhibitor effect on TNF-alpha pr oduction in titanium-stimulated monocytes. Pentoxifylline potentiated IL-6 and IL-1 production in monocytes exposed to titanium particles and had a bi phasic effect on the PGE(2) production. The results of this study support o ur hypothesis that human monocytes release bone resorption mediators after in vitro exposure to TiAlV alloy particles. The results also demonstrate th e differences of bone-resorbing mediators in response to different wear par ticle size. The pharmacologic agents (ciprofloxacin, pentoxifylline, and in domethacin) that can modulate the release of bone resorbing mediators such as PGE(2), TNF-alpha, IL-1, and IL-6 release from human monocytes. The resu lts help to elucidate the differences in cellular response to wear particle s but may not be directly transposed to the human situation. (C) 2000 John Wiley & Sons, Inc.