title: Acute inflammatory response to cobalt chromium orthopaedic wear debris in a rodent air-pouch model.
abstract: This study used a rodent air-pouch model to assess the acute inflammatory response to cobalt-chromium (CoCr) alloy wear debris from a metal-on-metal hip resurfacing implant that may contribute to joint failure. Air-pouches were injected with either sterile phosphate-buffered saline, 1 μg lipopolysaccharide (LPS) or 2.5 mg CoCr wear debris. The in situ inflammatory response was monitored 4, 24, 48 and 72 h and 7 days later. A flow cytometric analysis of the inflammatory exudates showed that CoCr wear debris induced a different inflammatory pattern compared with LPS. LPS induced a strong early (4 h) neutrophil influx, with monocyte/macrophage influx peaking at 24 h, whereas CoCr wear debris initiated almost equal numbers of early monocyte/macrophage and neutrophil recruitment. Histological analyses also showed CoCr debris accumulated in the pouch wall and this was accompanied by vast cellular infiltration and fibrosis around the debris throughout the duration of the experiment. Assessment of inflammatory gene transcripts from air-pouch tissue showed that CoCr wear debris increased the expression of cytokines involved in promoting inflammation and fibrosis (IL-1β, TGF-β) and chemokines that promote the recruitment of neutrophils and monocytes/macrophages (CXCL2 and CCL2). The data suggest that inflammatory responses to CoCr debris induce a specific acute process in which the recruitment of monocytes/macrophages is key.
authors.affiliation: Bioengineering Unit, University of Strathclyde, Wolfson Centre, Glasgow, UK.
authors.forename: Moeed
authors.initials: M
authors.lastname: Akbar
authors.forename: Alasdair R
authors.initials: AR
authors.lastname: Fraser
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Graham
authors.forename: James M
authors.initials: JM
authors.lastname: Brewer
authors.forename: M Helen
authors.initials: MH
authors.lastname: Grant
mesh_terms: D000818:Animals; D002858:Chromium Alloys / Q000009:adverse effects*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005355:Fibrosis; D006622:Hip Prosthesis / Q000009:adverse effects*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000378:metabolism* / Q000473:pathology; D011475:Prosthesis Failure / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D002858:Chromium Alloys; D016207:Cytokines; D008070:Lipopolysaccharides