Effects of cobalt and chromium ions on lymphocyte migration

A T cell-mediated hypersensitivity reaction has been reported in some patients with CoCrMo-based implants. However, the role of cobalt and chromium ions in this reaction remains unclear. The objective of the present study was to analyze the effects of Co²⁺ and Cr³⁺ in culture medium, as well as the effects of culture supernatants of macrophages exposed to Co²⁺ or Cr³⁺ , on the migration of lymphocytes. The release of cytokines/chemokines by macrophages exposed to Co²⁺ and Cr³⁺ was also analyzed. The migration of murine lymphocytes was quantified using the Boyden chamber assay and flow cytometry, while cytokine/chemokine release by J774A.1 macrophages was measured by ELISA. Results showed an ion concentration-dependent increase in TNF-α and MIP-1α release and a decrease in MCP-1 and RANTES release. Migration analysis showed that the presence of Co²⁺ (8 ppm) and Cr³⁺ (100 ppm) in culture medium increased the migration of T lymphocytes, while it had little or no effect on the migration of B lymphocytes, suggesting that Co²⁺ and Cr³⁺ can stimulate the migration of T but not B lymphocytes. Levels of T lymphocyte migration in culture medium containing Co²⁺ or Cr³⁺ were not statistically different from those in culture supernatants of macrophages exposed to Co²⁺ or Cr³⁺ , suggesting that the effects of the ions and chemokines were not additive, possibly because of ion interference with the chemokines and/or their cognate receptors. Overall, results suggest that Co²⁺ and Cr³⁺ are capable of stimulating the migration of T (but not B) lymphocytes in the absence of cytokines/chemokines, and could thereby contribute to the accumulation of more T than B lymphocytes in periprosthetic tissues of some patients with CoCrMo-based implants. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:916-924, 2017.