Drug inhibition of the macrophage response to metal wear particles in vitro.

Abstract:

:The wear particles of cobalt chrome alloy and titanium alloy have been implicated as a cause of aseptic loosening of prostheses. It is thought that their ability to induce either cell death or the release of mediators that induce bone resorption contributes to this loosening. This study was designed to test the hypothesis that these adverse biologic effects are due to wear particle corrosion at low pH after they have been phagocytosed by macrophages. Cobalt chrome alloy and titanium alloy particles of similar size and concentration to those found in the tissues surrounding failed prostheses were added to cultured rodent peritoneal macrophages. Treatment of macrophages with drugs that prevent a drop in pH within phagosomes significantly reduced the toxicity of phagocytosed cobalt chrome alloy particles. The same drugs also reduced the levels of prostaglandin E2 and interleukin-6 release induced by phagocytosed titanium alloy particles. When both types of particles were incubated at a low pH, similar to that encountered by phagocytosed particles, soluble products were released that induced the same effects as the particles themselves. These results show that enhanced corrosion of wear particles by phagocytic cells may contribute significantly to the adverse biologic effects of wear particles and identify drug therapies that may be investigated further.

journal_name

Clin Orthop Relat Res

authors

Haynes DR,Rogers SD,Howie DW,Pearcy MJ,Vernon-Roberts B

doi

10.1097/00003086-199602000-00045

subject

Has Abstract

pub_date

1996-02-01 00:00:00

pages

316-26

issue

323

eissn

0009-921X

issn

1528-1132

pub_type

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