Document Detail

The immunobiology of cobalt: demonstration of a potential aetiology for inflammatory pseudotumours after metal-on-metal replacement of the hip.
MedLine Citation:
PMID:  25183586     Owner:  NLM     Status:  In-Data-Review    
Abnormal wear of cobalt-containing metal-on-metal joints is associated with inflammatory pseudotumours. Cobalt ions activate human toll-like receptor 4 (TLR4), which normally responds to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4 by LPS increases the expression of chemokines IL-8 and CXCL10, which recruit leukocytes and activated T-cells, respectively. This study was designed to determine whether cobalt induces a similar inflammatory response to LPS by promoting the expression of IL-8 and CXCL10. A human monocytic cell line, derived from acute monocytic leukaemia, was treated with cobalt ions and expression of IL-8 and CXCL10 measured at mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold increase in IL-8 mRNA, and an eightfold increase in production of the mature chemokine (both p < 0.001); expression of the CXCL10 gene and protein was also significantly increased by cobalt (both p < 0.001). Experiments were also performed in the presence of CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated increase in IL-8 and CXCL10 expression. These findings suggest that cobalt ions induce inflammation similar to that observed during sepsis by the simultaneous activation of two TLR4-mediated signalling pathways. These pathways result in increased production of IL-8 and CXCL10, and may be implicated in pseudotumour formation following metal-on-metal replacement. Cite this article: Bone Joint J 2014; 96-B:1172-7.
H Lawrence; D Deehan; J Holland; J Kirby; A Tyson-Capper
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The bone & joint journal     Volume:  96-B     ISSN:  2049-4408     ISO Abbreviation:  Bone Joint J     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-09-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101599229     Medline TA:  Bone Joint J     Country:  England    
Other Details:
Languages:  eng     Pagination:  1172-7     Citation Subset:  AIM; IM    
Copyright Information:
©2014 The British Editorial Society of Bone & Joint Surgery.
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