Acute inflammatory response to cobalt chromium orthopaedic wear debris in a rodent air-pouch model

Akbar, M., Fraser, A. R., Graham, G. J. , Brewer, J. M. and Grant, M. H. (2012) Acute inflammatory response to cobalt chromium orthopaedic wear debris in a rodent air-pouch model. Journal of the Royal Society: Interface, 9(74), pp. 2109-2119. (doi: 10.1098/rsif.2012.0006)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Fraser, Dr Alasdair and Brewer, Professor James and Akbar, Mr Moeed and Graham, Professor Gerard
Authors: Akbar, M., Fraser, A. R., Graham, G. J., Brewer, J. M., and Grant, M. H.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Journal of the Royal Society: Interface
Publisher:The Royal Society
ISSN (Online):1742-5662
Published Online:18 April 2012
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
514422Regulation of the adaptive immune response by chemokine scavenging receptorsGerard GrahamMedical Research Council (MRC)G0901113III -IMMUNOLOGY