title: The effects of cobalt chromium upon macrophages.
abstract: The purpose of this study was to elucidate the mechanisms by which cobalt chromium particulate wear debris contribute to the aseptic loosening of total joint prostheses. Incubation of macrophages with cobalt chromium led to release of tumor necrosis factor-alpha (TNF-alpha) and prostaglandin E2 (PGE2), but did not lead to release of interleukin-1 beta (IL-1 beta) or interleukin 6 (IL-6). Exposure of macrophages cocultured with osteoblasts to cobalt chromium also led to significant release of TNF-alpha and PGE2, but did not lead to significant IL-6 or IL-1 beta production. The release of PGE2 in the coculture system was greater than that detected when macrophages were exposed to cobalt chromium without the osteoblast contribution. Exposure of radiolabeled calvaria to media from macrophages incubated with cobalt chromium in coculture with osteoblasts led to release of 45Ca. In contrast, exposure of radiolabeled calvaria to media from isolated macrophages incubated with these particles did not result in release of 45Ca. Exposure of macrophages to cobalt chromium was toxic, as reflected by release of the intracellular enzyme lactate dehydrogenase. Macrophages play a role in the initiation of bone resorption at the interface through the phagocytosis of cobalt chromium particles and subsequent release of TNF-alpha and PGE2. The presence of osteoblasts at the interface may be required for amplification of the inflammatory response and ultimately for bone resorption.
authors.affiliation: Department of Orthopaedic Surgery, Allegheny University Hospital, Philadelphia, Pennsylvania 19107, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Horowitz
authors.forename: W T
authors.initials: WT
authors.lastname: Luchetti
authors.forename: J B
authors.initials: JB
authors.lastname: Gonzales
authors.forename: C K
authors.initials: CK
authors.lastname: Ritchie
mesh_terms: D000818:Animals; D001862:Bone Resorption; D002461:Cell Line, Transformed; D002858:Chromium Alloys / Q000737:chemistry / Q000494:pharmacology*; D003035:Cobalt / Q000737:chemistry*; D003470:Culture Media; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009924:Organ Culture Techniques; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D002858:Chromium Alloys; D003470:Culture Media; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D003035:Cobalt; D007770:L-Lactate Dehydrogenase; D015232:Dinoprostone