Cutrale Perioperative and Ageing Group, Department of Bioengineering, Imperial College London, London, UK.
Computational Biology and Integrative Genomics, Department of Oncology, University of Oxford, Oxford, UK.
Sci Rep. 2022 Feb 9;12(1):2221. doi: 10.1038/s41598-022-06034-9.
Neuroinflammation after surgery and its contribution to peri-operative neurocognitive disorders (PND) is not well understood. Studying the association between central and peripheral cytokines and neuroinflammation is a prelude to the development of treatments for PND. Here, we investigate the hypotheses that there is a greater cytokine response in cerebrospinal fluid (CSF) than plasma after orthopaedic surgery, and that plasma cytokine levels are directly related to CSF cytokine levels, indicating that plasma cytokine levels may have potential as biomarkers of neuroinflammation. Patients admitted with a fractured neck of femur were invited to participate in this study. Participants had a spinal catheter inserted just prior to induction of anaesthesia. Samples of blood and CSF were taken before, immediately after, and on the first day following emergency surgery. The catheter was then removed. Samples were analysed for the presence of ten cytokines by immunoassay. A spinal catheter was successfully inserted in 11 participants during the 18-month study period. Five plasma cytokines (IL-4, IL-6, IL-10, IL-12p70 and IL-13) rose significantly following surgery, whereas all ten CSF cytokines rose significantly (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, IFN-γ and TNF-α) (adjusted-p < 0.05). Central (CSF) cytokine levels were consistently higher than their peripheral (plasma) counterparts after surgery, with some patients having a particularly marked neuroinflammatory response. The greatest increases occurred in IL-8 in CSF and IL-6 in plasma. There were significant, strong positive correlations between several of the measured cytokines in the CSF after surgery, but far fewer in plasma. There was no significant correlation between cytokine levels in the plasma and CSF at each of the three time points. To our knowledge, this is the first study to analyse paired samples of plasma and CSF for cytokine levels before and after emergency orthopaedic surgery. This study demonstrates that following surgery for a fractured neck of femur, there is a far greater rise in cytokines in the CSF compared to plasma. The lack of correlation between peripheral and central cytokines suggests measurement of peripheral cytokines are not necessarily related to which patients may have a large neuroinflammatory response.
手术后的神经炎症及其对围手术期神经认知障碍（PND）的影响尚不清楚。研究中枢和外周细胞因子与神经炎症之间的关系是开发 PND 治疗方法的前奏。在这里，我们假设在骨科手术后，脑脊液（CSF）中的细胞因子反应大于血浆，并且血浆细胞因子水平与 CSF 细胞因子水平直接相关，表明血浆细胞因子水平可能具有作为神经炎症生物标志物的潜力。我们邀请因股骨颈骨折入院的患者参与这项研究。参与者在接受麻醉诱导之前被插入脊髓导管。在紧急手术后立即抽取血液和 CSF 样本，并在手术后第一天抽取样本。然后取出导管。通过免疫测定法分析了 10 种细胞因子的存在。在 18 个月的研究期间，11 名参与者成功插入了脊髓导管。手术后，五种血浆细胞因子（IL-4、IL-6、IL-10、IL-12p70 和 IL-13）显着升高，而所有十种 CSF 细胞因子均显着升高（IL-1β、IL-2、IL-4、IL-6、IL-8、IL-10、IL-12p70、IL-13、IFN-γ和 TNF-α）（调整后 p < 0.05）。手术后中枢（CSF）细胞因子水平始终高于其外周（血浆）对应物，一些患者的神经炎症反应特别明显。最大的增加发生在 CSF 中的 IL-8 和血浆中的 IL-6。手术后 CSF 中几种测量的细胞因子之间存在显着的强正相关，但在血浆中则少得多。在三个时间点，血浆和 CSF 中的细胞因子之间没有显着相关性。据我们所知，这是第一项分析紧急骨科手术后血浆和 CSF 配对样本中细胞因子水平的研究。这项研究表明，在因股骨颈骨折接受手术后，CSF 中的细胞因子比血浆中的细胞因子升高得更多。外周和中枢细胞因子之间缺乏相关性表明，外周细胞因子的测量不一定与哪些患者可能具有较大的神经炎症反应有关。
