{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T05:44:32Z","timestamp":1793166272450,"version":"4.5.0"},"reference-count":41,"publisher":"British Editorial Society of Bone & Joint Surgery","issue":"9","license":[{"start":{"date-parts":[[2014,9,1]],"date-time":"2014-09-01T00:00:00Z","timestamp":1409529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/online.boneandjoint.org.uk\/TDM"}],"content-domain":{"domain":["online.boneandjoint.org.uk"],"crossmark-restriction":true},"short-container-title":["The Bone &amp; Joint Journal"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:p> 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 &lt; 0.001); expression of the CXCL10 gene and protein was also significantly increased by cobalt (both p &lt; 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. <\/jats:p><jats:p> 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. <\/jats:p><jats:p> Cite this article: Bone Joint J 2014; 96-B:1172\u20137. <\/jats:p>","DOI":"10.1302\/0301-620x.96b9.33476","type":"journal-article","created":{"date-parts":[[2014,9,2]],"date-time":"2014-09-02T14:23:37Z","timestamp":1409667817000},"page":"1172-1177","update-policy":"https:\/\/doi.org\/10.1302\/crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["The immunobiology of cobalt"],"prefix":"10.1302","volume":"96-B","author":[{"given":"H.","family":"Lawrence","sequence":"first","affiliation":[{"name":"Newcastle University, Institute\rof Cellular Medicine, 3rd Floor, William\rLeech Building, Faculty of Medical Sciences, Framlington\rPlace, Newcastle upon Tyne, NE2\r4HH, 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