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Cytokine release in mononuclear cells of patients with Co-Cr hip prosthesis
D Granchi1, G Ciapetti, S Stea
1Laboratory for Biocompatibility, Research on Implant Materials, Istituti Ortopedici Rizzoli, Bologna, Italy. donatella.granchi@ior.it
Insights
Cobalt-chromium hip implants release metal ions, causing increased TNF-alpha and decreased IL-6 in patients. This suggests a hypersensitivity reaction, potentially driven by Th1 lymphocytes, in aseptic loosening.
Area of Science:
- Biomaterials Science
- Immunology
- Orthopedic Surgery
Background:
- Aseptic loosening of metal-on-metal hip prostheses is a clinical challenge.
- Cobalt-chromium (Co-Cr) alloys are commonly used in hip implants.
- Understanding the immune response to metal ion release is crucial.
Purpose of the Study:
- To evaluate cytokine release from peripheral blood mononuclear cells (PBMC) in patients with aseptic loosening of Co-Cr hip prostheses.
- To investigate the effect of chromium and cobalt extracts on PBMC cytokine production.
- To correlate serum metal ion concentrations with immune responses.
Main Methods:
- Measurement of TNF-alpha, IL-6, and GM-CSF in unstimulated and stimulated PBMC.
- Culture of PBMC with chromium and cobalt extracts.
- Analysis of serum metal ion concentrations.
- Comparison between patients with Co-Cr implants and healthy controls.
Main Results:
- Unstimulated PBMC from patients showed higher TNF-alpha and lower IL-6 release compared to controls.
- Chromium and cobalt extracts significantly increased cytokine release in patient PBMC.
- Elevated serum metal ion concentrations correlated with increased TNF-alpha release.
- No significant differences in PBMC subpopulation proportions were observed.
Conclusions:
- Co-Cr implants release metal ions that may trigger or sustain cell-mediated hypersensitivity.
- Increased TNF-alpha and decreased IL-6 in patients suggest a Th1-dominant immune response.
- These findings provide insights into the mechanisms of aseptic loosening in Co-Cr hip prostheses.
Abstract:
The aim of this study was the evaluation of the release of bone-resorbing cytokines in peripheral blood mononuclear cells (PBMC) of patients with aseptic loosening of Co-Cr hip prostheses. TNF-alpha, IL-6, and GM-CSF were measured in both unstimulated and PHA-stimulated PBMC, and in PBMC cultured in the presence of chromium and cobalt extracts. Blood samples from healthy donors were used as controls. Serum samples of both patients and healthy donors were tested to determine the concentration of metal ions. The proportion of lymphocyte, monocyte and lympocyte subpopulation in cultured PBMC did not differ in patients and the control group. In unstimulated PBMC the release of TNF was significantly higher in patients than in the control group, while IL-6 was significantly decreased and no change was observed for GM-CSF. When the PBMC were challenged with chromium extract, all the 'index of cytokine release' resulted higher in patients than in the control group; cobalt extract increased both the TNF and GM-CSF index, but not the index of IL-6 release. Metal concentrations in serum from patients were significantly increased and correlated with the TNF release in PBMC stimulated with both metal extract. Our results suggest that a CoCr-implant releases a large amount of metal ions which could mediate the priming or the renewal of a cell-mediated hypersensitivity reaction. The prevalence of circulating lymphocytes responsible for the delayed hypersensitivity, namely Thl, would justify both the significant increase of TNF and the significant decrease of IL6 in unstimulated PBMC of patients, as well as the significant increase of the 'index of cytokine release' after the challenge with metal ions.