DRUG-INHIBITION OF THE MACROPHAGE RESPONSE TO METAL WEAR PARTICLES IN-VITRO

The wear particles of cobalt chrome alloy and titanium alloy have been implicated as a cause of aseptic loosening of prostheses, It is thoug ht that their ability to induce either cell death or the release of me diators that induce bone resorption contributes to this loosening, Thi s study was designed to test the hypothesis that these adverse biologi c effects are due to wear particle corrosion at low pH after they have been phagocytosed by macrophages, Cobalt chrome alloy and titanium al loy particles of similar size and concentration to those found in the tissues surrounding failed prostheses were added to cultured rodent pe ritoneal 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 reduce d the levels of prostaglandin E(2) and interleukin-6 release induced b y phagocytosed titanium alloy particles, When both types of particles were incubated at a low pH, similar to that encountered by phagocytose d particles, soluble products were released that induced the same effe cts as the particles themselves, These results show that enhanced corr osion of wear particles by phagocytic cells may contribute significant ly to the adverse biologic effects of wear particles and identify drug therapies that may be investigated further.