Posada Olga M, Tate R J, Grant M H
Biomedical Engineering Department, University of Strathclyde, Wolfson Centre, Glasgow, UK.
J Appl Toxicol. 2015 Jun;35(6):614-22. doi: 10.1002/jat.3100. Epub 2015 Jan 21.
Adverse tissue responses to prostheses wear particles and released ions are important contributors to hip implant failure. In implant-related adverse reactions T-lymphocytes play a prominent role in sustaining the chronic inflammatory response. To further understand the involvement of lymphocytes in metal-on-metal (MoM) implant failure, primary human lymphocytes were isolated and treated with cobalt-chromium (Co-Cr) wear debris and Co ions, individually, and in combination, for 24, 48 and 120 h. There was a significant increase in cell number where debris was present, as measured by the Neutral Red assay. Interleukin-6 (IL-6), interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) secretion levels significantly decreased in the presence of metal particles, as measured by ELISA. Interleukin-2 (IL-2) secretion levels were significantly decreased by both debris and Co ions. Flow cytometry analysis showed that the metal nanoparticles induced a significant increase in apoptosis after 48-h exposure. This investigation showed that prolonged exposure (120 h) to metal debris induces lymphocyte proliferation, suggesting that activation of resting lymphocytes may have occurred. Although cytokine production was affected mainly by metal debris, cobalt toxicity may also modulate IL-2 secretion, and even Co ion concentrations below the MHRA guideline levels (7 ppb) may contribute to the impairment of immune regulation in vivo in patients with MoM implants.
假体磨损颗粒和释放离子引起的组织不良反应是髋关节植入物失败的重要原因。在与植入物相关的不良反应中,T淋巴细胞在维持慢性炎症反应中起重要作用。为了进一步了解淋巴细胞在金属对金属(MoM)植入物失败中的作用,分离了原代人淋巴细胞,分别用钴铬(Co-Cr)磨损碎片和Co离子单独及联合处理24、48和120小时。通过中性红试验测量,存在碎片的情况下细胞数量显著增加。通过酶联免疫吸附测定法(ELISA)测量,在存在金属颗粒的情况下,白细胞介素-6(IL-6)、干扰素-γ(IFN-γ)和肿瘤坏死因子-α(TNF-α)的分泌水平显著降低。碎片和Co离子均显著降低白细胞介素-2(IL-2)的分泌水平。流式细胞术分析表明,金属纳米颗粒在暴露48小时后诱导细胞凋亡显著增加。本研究表明,长时间暴露(120小时)于金属碎片会诱导淋巴细胞增殖,这表明静息淋巴细胞可能发生了激活。虽然细胞因子的产生主要受金属碎片影响,但钴的毒性也可能调节IL-2的分泌,甚至低于药品和医疗产品监管局(MHRA)指导水平(7 ppb)的Co离子浓度也可能导致MoM植入物患者体内免疫调节受损。