The molecular mechanism of cell activation by cobalt ions. Comment on Ninomiya et al.: Metal ions activate vascular endothelial cells and increase lymphocyte chemotaxis and binding

Dear Editors: We read the recent paper by Ninomiya et al. with considerable interest and share the authors conclusion that cobalt ions released by orthopaedic metals can directly activate cells leading to the release of proinflammatory chemokines. Although Ninomiya et al. argue against a “need for immunological sensitization by metal ions,” thereby excluding the adaptive immune response, the biological basis for the innate immune response to cobalt ions was not identified. Our group has recently demonstrated that clinically relevant concentrations of cobalt ions can activate human toll-like receptor 4 (TLR4) in a manner entirely analogous to innate immune recognition of the bacterial endotoxin, lipopolysaccharide. Downstream consequences of the activation of this receptor include the release of multiple pro-inflammatory cytokines (including chemokines) and upregulation of the expression of immunologically relevant adhesion molecules. We feel that the work of our group and others 3,4 in this important area provide a clear basis to explain the observations reported in this journal by Ninomiya et al. Further studies will certainly lead to the development of strategies to mitigate the innate immune response to cobalt ions, allowing safer use of metal-on-metal bearings in arthroplasty.