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Effect of anti-inflammatory medication on monocyte response to titanium particles
1Department of Orthopedic Surgery, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, Taiwan, 10002, Republic of China.
Abstract:
Cytokines produced by macrophages in the periprosthetic membranes surrounding joint replacements have been implicated as causal agents in osteolysis and prosthetic loosening. The present study characterizes the response of human peripheral blood monocytes to titanium particles. Monocytes were obtained from donated blood and were cultured in the presence of different-sized titanium particles. Exposure to titanium-aluminum-vanadium particles significantly changed the release of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 (IL-1), whereas there was no significant effect on the release of prostaglandin E(2) (PGE(2)). When monocytes were cultured with particles, the titanium alloy particles induced significantly more release of TNF-alpha and less IL-1 secretion. Ciprofloxacin inhibited production of TNF-alpha, IL-6, IL-1, and PGE(2) in human monocytes exposed to titanium particles. In contrast to ciprofloxacin, indomethacin was not a potent inhibitor of TNF-alpha production but potentiated IL-6 production in titanium-stimulated monocytes. Indomethacin had no effect on the production of IL-1 and was a potent inhibitor of PGE(2) production in titanium-stimulated monocytes. Pentoxifylline had an inhibitor effect on TNF-alpha production in titanium-stimulated monocytes. Pentoxifylline potentiated IL-6 and IL-1 production in monocytes exposed to titanium particles and had a biphasic effect on the PGE(2) production. The results of this study support our hypothesis that human monocytes release bone resorption mediators after in vitro exposure to TiAlV alloy particles. The results also demonstrate the differences of bone-resorbing mediators in response to different wear particle size. The pharmacologic agents (ciprofloxacin, pentoxifylline, and indomethacin) 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 results help to elucidate the differences in cellular response to wear particles but may not be directly transposed to the human situation.
Insights
Human monocytes release bone-resorbing mediators when exposed to titanium particles, potentially causing implant loosening. Certain drugs like ciprofloxacin can inhibit this response, offering insights into managing periprosthetic osteolysis.
Area of Science:
- Biomaterials Science
- Immunology
- Orthopedic Surgery
Background:
- Periprosthetic osteolysis and implant loosening are linked to cytokines released by macrophages interacting with joint replacement materials.
- Understanding the cellular response to wear particles is crucial for improving implant longevity.
Purpose of the Study:
- To characterize the in vitro response of human peripheral blood monocytes to titanium particles.
- To investigate the effects of different-sized titanium particles on cytokine and prostaglandin release.
- To evaluate the modulatory effects of ciprofloxacin, indomethacin, and pentoxifylline on these responses.
Main Methods:
- Human peripheral blood monocytes were isolated and cultured with varying sizes of titanium-aluminum-vanadium (TiAlV) particles.
- The release of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), interleukin-1 (IL-1), and prostaglandin E(2) (PGE(2)) was measured.
- The impact of ciprofloxacin, indomethacin, and pentoxifylline on mediator release was assessed.
Main Results:
- Exposure to TiAlV particles significantly altered TNF-alpha, IL-6, and IL-1 release, but not PGE(2).
- Titanium alloy particles induced greater TNF-alpha and lower IL-1 release.
- Ciprofloxacin inhibited all measured mediators, while indomethacin and pentoxifylline showed differential effects on cytokine and PGE(2) production.
Conclusions:
- Human monocytes release bone resorption mediators upon in vitro exposure to TiAlV particles.
- The study highlights differential mediator release in response to particle size and the potential of pharmacologic agents to modulate these responses.
- Findings provide insights into cellular responses to wear particles, though direct clinical translation requires further investigation.
