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缺血性中风患者唾液中促炎、抗炎、Th1、Th2和Th17细胞因子的筛查评估

The screening assessment of pro-inflammatory, anti-inflammatory, Th1, Th2 and Th17 cytokines in saliva of patients with ischemic stroke.

作者信息

Forszt Dominika, Gerreth Karolina, Kopczyński Jakub, Zalewska Anna, Hojan Katarzyna, Marchewka Renata, Bielas Marzena, Maciejczyk Mateusz

机构信息

Department of Risk Group Dentistry, Pediatric Dentistry, Poznan University of Medical Sciences, Poznan, Poland.

Department of Risk Group Dentistry, Chair of Pediatric Dentistry, Poznan University of Medical Sciences, Poznan, Poland.

出版信息

Int J Med Sci. 2025 May 28;22(11):2686-2699. doi: 10.7150/ijms.110452. eCollection 2025.

Abstract

Ischemic stroke leads to hypoxia of brain structures, causes inflammation and tissue necrosis. Since the blood-brain barrier is damaged, inflammatory mediators can enter the bloodstream and saliva. This case-control study examines pro-inflammatory, anti-inflammatory, Th1, and Th2 cytokines in the unstimulated saliva of stroke patients and explores the association between these biomarkers and clinical status. The study group included 22 patients with ischemic stroke, while the control group included 22 healthy individuals that were matched for age, sex, dental, periodontal and oral hygiene status to the study group. Unstimulated saliva was collected from each patient. In each sample, the inflammatory profile was determined using the multiplex ELISA method. Due to the lack of normal distribution, the Mann-Whitney U test was used for comparisons. The research was approved by the Bioethics Committee of the Poznan University of Medical Sciences (59/19, 890/19, 504/21). In the unstimulated saliva of stroke patients, significantly higher levels of pro-inflammatory cytokines (IL-1β (p=0.0003), TNF-α (p≤0.0001), TNF-β; (p≤0.0001)), anti-inflammatory cytokines (IL-1ra (p≤0.0001), TRAIL (p=0.0206)), Th1 cytokines (IFN- (p≤0.0001), IL-2Rα (p=0.0021) and IL-12 (p40) (p≤0.0001)) and Th2 cytokines (IL-6 (p=0.0023)) were found compared to healthy participants. Interestingly, Addenbrooke's Cognitive Examination Revised (ACE-R) correlated negatively with TNF-α (p=0.01, r=-0.53), TNF-β (p=0.02, r=-0.60) and IFN-γ (p=0.02, r=-0.50). The Functional Independence Measure (FIM) exhibited a positive association with IL-6 (p=0.003, r=0.62) and BI (p=0.001, r=0.66). The positive correlation was found between Sitting Balance Scale (SBS) and IL-6 (p=0.02, r=0.52). Stroke patients exhibit altered salivary composition characterized by increased secretion of inflammatory mediators. The obtained results do not indicate the dominance of any of the branches of the immune response. The concentration of salivary TNF-α, TNF-β, IFN- and IL-12 significantly distinguish patients with ischemic stroke from healthy individuals. Although validation of the results in a larger patient population is necessary, salivary cytokines show potential as diagnostic biomarkers.

摘要

缺血性中风会导致脑结构缺氧,引发炎症和组织坏死。由于血脑屏障受损,炎症介质可进入血液和唾液。本病例对照研究检测了中风患者非刺激性唾液中的促炎、抗炎、Th1和Th2细胞因子,并探讨了这些生物标志物与临床状态之间的关联。研究组包括22例缺血性中风患者,对照组包括22名年龄、性别、牙齿、牙周和口腔卫生状况与研究组匹配的健康个体。从每位患者采集非刺激性唾液。在每个样本中,使用多重ELISA方法测定炎症谱。由于数据缺乏正态分布,采用曼-惠特尼U检验进行比较。该研究经波兹南医科大学伦理委员会批准(59/19, 890/19, 504/21)。与健康参与者相比,中风患者的非刺激性唾液中促炎细胞因子(IL-1β(p = 0.0003)、TNF-α(p≤0.0001)、TNF-β;(p≤0.0001))、抗炎细胞因子(IL-1ra(p≤0.0001)、TRAIL(p = 0.0206))、Th1细胞因子(IFN-(p≤0.0001)、IL-2Rα(p = 0.0021)和IL-12(p40)(p≤0.0001))和Th2细胞因子(IL-6(p = 0.0023))水平显著更高。有趣的是,修订后的Addenbrooke认知检查(ACE-R)与TNF-α(p = 0.01,r = -0.53)、TNF-β(p = 0.02,r = -0.60)和IFN-γ(p = 0.02,r = -0.50)呈负相关。功能独立性测量(FIM)与IL-6(p = 0.003,r = 0.62)和BI(p = 0.001,r = 0.66)呈正相关。坐位平衡量表(SBS)与IL-6呈正相关(p = 0.02,r = 0.52)。中风患者的唾液成分发生改变,其特征为炎症介质分泌增加。所得结果并未表明免疫反应的任何分支占主导地位。唾液中TNF-α、TNF-β、IFN-和IL-12的浓度可显著区分缺血性中风患者与健康个体。尽管有必要在更大的患者群体中验证结果,但唾液细胞因子显示出作为诊断生物标志物具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5886/12163425/5934f4f74c23/ijmsv22p2686g001.jpg

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