Bandyopadhyay Soham, Gaastra Ben, Zolnourian Ardalan, Garland Patrick, Wu Chieh-Hsi, Galea Ian, Bulters Diederik
Clinical Neurosciences, Clinical & Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, Hampshire, UK.
Wessex Neurological Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
Transl Stroke Res. 2025 Mar 25. doi: 10.1007/s12975-025-01348-y.
Neuroinflammation may contribute to outcomes following subarachnoid haemorrhage (SAH). Human cerebrospinal fluid (CSF) cytokine data is limited and its relationship with systemic inflammation is unknown. This study compares the inflammatory responses in CSF and plasma compartments, and their associations with outcome.
Ten cytokines were measured in CSF and plasma from 98 SAH patients and 18 control patients. Outcome was assessed with the modified Rankin scale (mRS) and Subarachnoid Haemorrhage Outcome Tool (SAHOT) at days 7, 28, 90 and 180. Regression analyses and principal component analysis (PCA) were performed.
Median levels of all CSF cytokines and plasma IL-6 were higher in SAH patients than controls (p < 0.001). Plasma IL-6 peaked earlier (3 days after SAH) than CSF cytokines (7-9 days after SAH). On day 7, CSF levels were greater than plasma levels for all cytokines (p < 0.001). There was no correlation between individual cytokines in the plasma and CSF. Only plasma IL-6 levels correlated with long-term outcome (mRS (p = 0.009) and SAHOT (p = 0.007) at day 180), accounting for WFNS and blood volume. Seven principal components of cytokines had an eigenvalue greater than 1. Only the first plasma principal component (dominated by IL-6, IL-8, IL-12, IL-13, and TNF-α) was associated with outcomes (p < 0.05). Mediation analysis suggested the effects of WFNS and blood volume on outcome were not mediated by IL-6 or this principal component.
SAH provokes an inflammatory response in CSF and plasma. The response pattern is different and distinct in each compartment. Each compartment's relationship with outcomes differ, suggesting separate roles in SAH pathophysiology. Plasma IL-6 is independently associated with outcomes.
神经炎症可能会影响蛛网膜下腔出血（SAH）后的预后。人类脑脊液（CSF）细胞因子数据有限，其与全身炎症的关系尚不清楚。本研究比较了脑脊液和血浆中炎症反应及其与预后的关联。
对98例SAH患者和18例对照患者的脑脊液和血浆中的10种细胞因子进行检测。在第7、28、90和180天，采用改良Rankin量表（mRS）和蛛网膜下腔出血预后工具（SAHOT）评估预后。进行回归分析和主成分分析（PCA）。
SAH患者脑脊液中所有细胞因子和血浆白细胞介素-6（IL-6）的中位数水平均高于对照组（p<0.001）。血浆IL-6峰值出现时间早于脑脊液细胞因子（SAH后3天对比SAH后7 - 9天）。在第7天，所有细胞因子的脑脊液水平均高于血浆水平（p<0.001）。血浆和脑脊液中的单个细胞因子之间无相关性。仅血浆IL-6水平与长期预后相关（第180天mRS（p = 0.009）和SAHOT（p = 0.007）），并考虑了世界神经外科联盟（WFNS）分级和出血量。细胞因子的七个主成分特征值大于1。仅第一个血浆主成分（以IL-6、IL-8、IL-12、IL-13和肿瘤坏死因子-α（TNF-α）为主）与预后相关（p<0.05）。中介分析表明，WFNS分级和出血量对预后的影响并非由IL-6或该主成分介导。
SAH可引发脑脊液和血浆中的炎症反应。各腔室的反应模式不同且有差异。每个腔室与预后的关系不同，提示在SAH病理生理过程中发挥不同作用。血浆IL-6与预后独立相关。
