The effect of chromium and cobalt ions on primary human lymphocytes in vitro

Moeed Akbar, James M. Brewer, M. Helen Grant

    Research output: Contribution to journalArticle

    57 Citations (Scopus)

    Abstract

    Cobalt-chromium (Co-Cr) alloy metal-on-metal hip resurfacing is increasingly common among younger more active patients suffering from osteoarthritis. Recent reports have increased awareness of metal ions leaching from metallic articulations; this ion exposure may have adverse effects on the immune system. As previous studies reported alterations in lymphocyte number and function in patients with Co-Cr implants, we investigated effects of clinically relevant concentrations of Cr6+ and Co2+ on primary human lymphocytes in vitro. Here, both resting and activated (anti-CD3 ± anti-CD28 antibodies) primary human lymphocytes were exposed to Cr6+ or Co2+ (0.1–100 µM). Following 24 or 48 h of exposure, cell viability, proliferation, cytokine [interferon-γ (IFNγ and interleukin-2 (IL-2)] release, and apoptosis (with and without pre-treatment of cells with a caspase-3 inhibitor) were assessed. Exposure to 10 and 100 µM Cr6+ significantly decreased cell viability and increased apoptosis in both resting and activated lymphocytes. Cell proliferation and cytokine release were also significantly reduced in activated lymphocytes following exposure. The exposure of resting lymphocytes to 100 µM Co2+ resulted in significant decreases in cell viability accompanied by a significant increase in apoptosis. Activated lymphocytes also showed this response after exposure to 100 µM Co2+; in fact, activated cells were significantly more sensitive to Co2+ toxicity. Exposure to 10 µM Co2+ led to significant decreases in cell proliferation and cytokine release, but no significant increase in apoptosis, in activated cells. The results indicate that exposure to high concentrations of metal ions initiate apoptosis that results in decreased lymphocyte proliferation. IL-2 release is inhibited by both metal ions at concentrations that are not overtly toxic. However, metal ion concentrations not directly cytotoxic to lymphocytes may affect events at a molecular level, thereby impeding lymphocyte proliferation. Hence, this may contribute to altered immune system function in patients with Co-Cr implants.
    Original languageEnglish
    Pages (from-to)140-149
    Number of pages10
    JournalJournal of Immunotoxicology
    Volume8
    Issue number2
    DOIs
    Publication statusPublished - Jun 2011

    Fingerprint

    Lymphocytes
    Chromium
    Cobalt
    Ions
    Metals
    Apoptosis
    Metal ions
    Cell proliferation
    Cell Survival
    Cell Proliferation
    Cytokines
    Immune system
    Cells
    Interleukin-2
    Immune System
    Chromium Alloys
    In Vitro Techniques
    Caspase Inhibitors
    Poisons
    Lymphocyte Count

    Keywords

    • chromium
    • cobalt
    • apoptosis
    • lymphocyte
    • ions
    • metal implant
    • in vitro

    Cite this

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    title = "The effect of chromium and cobalt ions on primary human lymphocytes in vitro",
    abstract = "Cobalt-chromium (Co-Cr) alloy metal-on-metal hip resurfacing is increasingly common among younger more active patients suffering from osteoarthritis. Recent reports have increased awareness of metal ions leaching from metallic articulations; this ion exposure may have adverse effects on the immune system. As previous studies reported alterations in lymphocyte number and function in patients with Co-Cr implants, we investigated effects of clinically relevant concentrations of Cr6+ and Co2+ on primary human lymphocytes in vitro. Here, both resting and activated (anti-CD3 ± anti-CD28 antibodies) primary human lymphocytes were exposed to Cr6+ or Co2+ (0.1–100 µM). Following 24 or 48 h of exposure, cell viability, proliferation, cytokine [interferon-γ (IFNγ and interleukin-2 (IL-2)] release, and apoptosis (with and without pre-treatment of cells with a caspase-3 inhibitor) were assessed. Exposure to 10 and 100 µM Cr6+ significantly decreased cell viability and increased apoptosis in both resting and activated lymphocytes. Cell proliferation and cytokine release were also significantly reduced in activated lymphocytes following exposure. The exposure of resting lymphocytes to 100 µM Co2+ resulted in significant decreases in cell viability accompanied by a significant increase in apoptosis. Activated lymphocytes also showed this response after exposure to 100 µM Co2+; in fact, activated cells were significantly more sensitive to Co2+ toxicity. Exposure to 10 µM Co2+ led to significant decreases in cell proliferation and cytokine release, but no significant increase in apoptosis, in activated cells. The results indicate that exposure to high concentrations of metal ions initiate apoptosis that results in decreased lymphocyte proliferation. IL-2 release is inhibited by both metal ions at concentrations that are not overtly toxic. However, metal ion concentrations not directly cytotoxic to lymphocytes may affect events at a molecular level, thereby impeding lymphocyte proliferation. Hence, this may contribute to altered immune system function in patients with Co-Cr implants.",
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    The effect of chromium and cobalt ions on primary human lymphocytes in vitro. / Akbar, Moeed; Brewer, James M.; Grant, M. Helen.

    In: Journal of Immunotoxicology, Vol. 8, No. 2, 06.2011, p. 140-149.

    Research output: Contribution to journalArticle

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