The immunobiology of cobalt: demonstration of a potential aetiology for inflammatory pseudotumours after metal-on-metal replacement of the hip

Bone Joint J. 2014 Sep;96-B(9):1172-7. doi: 10.1302/0301-620X.96B9.33476.


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.

Keywords: CXCL10; Cobalt; Hip replacement; IL-8; Metal-on-metal; TLR4.

Publication types

  • Evaluation Study

MeSH terms

  • Biomarkers / metabolism
  • Cell Line
  • Chemokine CXCL10 / metabolism
  • Cobalt / immunology*
  • Enzyme-Linked Immunosorbent Assay
  • Granuloma, Plasma Cell / etiology*
  • Granuloma, Plasma Cell / immunology
  • Hip Prosthesis / adverse effects*
  • Humans
  • Interleukin-8 / metabolism
  • Joint Diseases / etiology*
  • Joint Diseases / immunology
  • Lipopolysaccharides / immunology
  • Macrophages / metabolism
  • Metal-on-Metal Joint Prostheses / adverse effects*
  • Monocytes / metabolism
  • Toll-Like Receptor 4 / metabolism


  • Biomarkers
  • CXCL10 protein, human
  • Chemokine CXCL10
  • Interleukin-8
  • Lipopolysaccharides
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Cobalt