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Cytokine and Eicosanoid Production by Cultured Human Monocytes Exposed to Titanium Particulate Debris

Published online by Cambridge University Press:  08 August 2002

Timothy M. Robinson
Affiliation:
Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison
Paul A. Manley
Affiliation:
Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison
Paul A. Sims
Affiliation:
Department of Animal Health and Biomedical Science, School of Veterinary Medicine, University of Wisconsin-Madison
Ralph Albrecht
Affiliation:
Department of Animal Health and Biomedical Science, School of Veterinary Medicine, University of Wisconsin-Madison
Benjamin J. Darien
Affiliation:
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison
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Abstract

Phagocytosis of particulate wear debris from arthroplasties by macrophages induces an inflammatory response that has been linked to implant loosening and premature failure of artificial joints. Inflammatory mediators released by phagocytic macrophages such as tumor necrosis factor-a (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and prostaglandin E2 (PGE2) are believed to play a central role in the pathogenesis of aseptic loosening. The objective of this study was to characterize titanium alloy particulates that closely match wear debris found around joint arthroplasties and to study their effects on the biosynthesis of inflammatory mediators by cultured monocytes. Peripheral blood monocytes were isolated from healthy human volunteers. Monocytes were cultured in 96-well plates for 24 h, washed, and exposed to three concentrations of titanium particulates and controls from 18Ð24 h. Supernatants were assayed for TNF-α, IL-1β, IL-6, and PGE2 activity. Energy dispersive X-ray spectroscopy (EDX) verified the titanium alloy to be Ti6A14V. Scanning electron microscopy (SEM) analysis showed significant titanium particulate heterogeneity with approximately 95% of the particles <1 micrometer in diameter. SEM and EDX technology was useful in the characterization of the titanium particulates utilized for in vitro models of titanium-induced cytokine release by monocytes. Incubation of titanium particulates (in concentrations similar to those found around loosened prosthetic joints) with cultured monocytes significantly increased their production of TNF-α, IL-1β, and PGE2.

Type
Articles
Copyright
© 1999 Microscopy Society of America

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