Department of Molecular Neuropharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Intelliseq sp. z o.o, Krakow, Poland.
Transl Psychiatry. 2021 Apr 26;11(1):246. doi: 10.1038/s41398-021-01359-x.
Altered cytokine synthesis thought to contribute to the pathophysiology of post-stroke depression (PSD). Toll-like receptor 4 (TLR4) is a master regulator of innate immunity. The aim of this study was to explore the putative association between TLR4-mediated cytokine synthesis and subsequent symptoms of PSD. In total, 262 patients with ischemic stroke and without a history of PSD were included. Depressive symptoms were assessed using the Patient Health Questionnaire-9 in 170 patients on Day 8 and in 146 at 3 months after stroke. Blood samples taken on Day 3 after stroke were stimulated ex vivo with lipopolysaccharide (LPS). Ex vivo synthesized cytokines (TNFα, IP-10, IL-1β, IL-6, IL-8, IL-10, and IL-12p70) and circulating cytokines (TNFα, IL-6, sIL-6R, and IL-1ra) were measured using the enzyme-linked immunoassay or cytometric method. RNA sequencing was used to determine the gene expression profile of LPS-induced cytokines and chemokines. LPS-induced cytokine synthesis and the gene expression of TLR4-dependent cytokines and chemokines did not differ between patients with and without greater depressive symptoms. The plasma level of IL-6, but not TNFα, sIL-6R, and IL-1ra, was higher in patients who developed depressive symptoms at 3 months after stroke (median: 4.7 vs 3.4 pg/mL, P = 0.06). Plasma IL-6 predicted the severity of depressive symptoms at 3 months after stroke (β = 0.42, P = 0.03). In conclusion, TLR4-dependent cytokine synthesis was not associated with greater post-stroke depressive symptoms in this study. Circulating IL-6 might be associated with depressive symptoms occurring at 3 months after stroke.
据认为，细胞因子合成的改变有助于中风后抑郁（PSD）的病理生理学。 Toll 样受体 4（TLR4）是先天免疫的主要调节剂。本研究旨在探讨 TLR4 介导的细胞因子合成与随后 PSD 症状之间的可能关联。共有 262 名缺血性中风且无 PSD 病史的患者入组。在中风后第 8 天对 170 名患者和 3 个月时对 146 名患者使用患者健康问卷-9 评估抑郁症状。中风后第 3 天采集血样，体外用脂多糖（LPS）刺激。使用酶联免疫吸附试验或细胞仪法检测体外合成的细胞因子（TNFα、IP-10、IL-1β、IL-6、IL-8、IL-10 和 IL-12p70）和循环细胞因子（TNFα、IL-6、sIL-6R 和 IL-1ra）。使用 RNA 测序确定 LPS 诱导的细胞因子和趋化因子的基因表达谱。有或无更严重抑郁症状的患者之间，LPS 诱导的细胞因子合成以及 TLR4 依赖性细胞因子和趋化因子的基因表达无差异。中风后 3 个月出现抑郁症状的患者的血浆 IL-6 水平（中位数：4.7 与 3.4 pg/mL，P=0.06）高于无抑郁症状的患者，而 TNFα、sIL-6R 和 IL-1ra 水平无差异。血浆 IL-6 可预测中风后 3 个月时抑郁症状的严重程度（β=0.42，P=0.03）。总之，在本研究中，TLR4 依赖性细胞因子合成与中风后更严重的抑郁症状无关。循环 IL-6 可能与中风后 3 个月发生的抑郁症状有关。
