Cytokines produced by leukocytes in the periprosthetic membranes surrounding joint replacements have been implicated as causal agents in osteolysis and prosthetic loosening. In this study, we used an in vitro leukocyte culture system to monitor the response of leukocytes to various metal ions and their possible roles in the mechanism of aseptic loosening. Human peripheral leukocytes were isolated and incubated with various concentrations of Co2+, Cr3+, and Ti3+ ions. Leukocyte cell counts and the levels of the tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) and prostaglandin E2 (PGE2) released into the media were analyzed at 1 h, 3 h, and 1, 3, and 7 day intervals. The results showed that adding different metal ions into leukocyte cultures did not affect the cell counts. Exposure of leukocytes to Co2+ ion increased the release of TNF-α, IL-6, and PGE2. Exposure of leukocytes to Cr3+ ion did not increase the release of TNF-α but increased the secretion of IL-6 and PGE2. In contrast, exposure of the leukocytes to Ti3+ ions was associated with a decrease in the release of TNF-α and PGE2 and a minimal change in IL-6 noted after 7 days' culture. The present study elucidated the possible mechanisms involved in periprosthetic osteolysis and the inflammatory response of human leukocytes to metal ions. We found that cobalt ion is the most potent stimulant for cytokines and prostaglandin secretion by leukocytes. This elucidation, in combination with other efforts to reduce the generation of wear debris and metal ions, may improve the longevity of orthopedic implants.
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