Central Laboratory, Department of Neurology, Fu Xing Hospital, Capital Medical University, Beijing 100038, China.
Central Laboratory, Department of Neurology, Fu Xing Hospital, Capital Medical University, Beijing 100038, China.
Cytokine. 2024 Oct;182:156713. doi: 10.1016/j.cyto.2024.156713. Epub 2024 Jul 29.
Previous observational studies have reported the correlation between circulating inflammatory cytokines and cerebral small vessel disease (CSVD). However, the causality of this association is uncertain. This study used Mendelian randomization to investigate the causal effect of circulating inflammatory cytokines on neuroimaging changes in CSVD.
This study utilized genetic variances of 41 inflammatory cytokines and 3 neuroimaging markers of CSVD from genome-wide association studies to assess the causal effects in a two-sample Mendelian randomization approach. Inverse variance weighted analysis was used as the main analytical method, and sensitivity analysis was used to further validate the robustness of the results.
Increased IL-18 was associated with increased white matter hyperintensity (WMH) and mean diffusivity (MD) (β = 0.034, 95 % CI 0.002, 0.065, P=0.038, β = 0.157, 95 % CI 0.015, 0.299, P=0.030). However, increased IL-18 was associated with decreased fractional anisotropy (FA) (β = -0.141, 95 % CI -0.279, -0.002, P=0.047). Increased monocyte chemotactic protein-1(MCP-1) was associated with decreased FA (β = -0.278, 95 % CI -0.502, -0.054, P=0.015). Increased IL-10 levels and IL-2ra levels were associated with decreased risks of MD (β = -0.228, 95 % CI -0.448, -0.009, p = 0.041; β = -0.204, 95 % CI=-0.377, -0.031, p = 0.021).
This study revealed that increased levels of IL-18 and MCP-1 were associated with white matter microstructural injury, and increased levels of IL-10 and IL-2ra were associated with decreased MD.
先前的观察性研究报告了循环炎症细胞因子与脑小血管疾病（CSVD）之间的相关性。然而，这种关联的因果关系尚不确定。本研究使用孟德尔随机化来研究循环炎症细胞因子对 CSVD 神经影像学变化的因果影响。
本研究利用全基因组关联研究中 41 种炎症细胞因子和 3 种 CSVD 神经影像学标志物的遗传方差，采用两样本孟德尔随机化方法评估因果效应。采用逆方差加权分析作为主要分析方法，并采用敏感性分析进一步验证结果的稳健性。
白细胞介素 18（IL-18）水平升高与脑白质高信号（WMH）和平均弥散度（MD）增加相关（β=0.034，95%CI：0.002，0.065，P=0.038，β=0.157，95%CI：0.015，0.299，P=0.030）。然而，白细胞介素 18（IL-18）水平升高与分数各向异性（FA）降低相关（β=-0.141，95%CI：-0.279，-0.002，P=0.047）。单核细胞趋化蛋白 1（MCP-1）水平升高与 FA 降低相关（β=-0.278，95%CI：-0.502，-0.054，P=0.015）。白细胞介素 10（IL-10）和白细胞介素 2 受体α（IL-2ra）水平升高与 MD 风险降低相关（β=-0.228，95%CI：-0.448，-0.009，P=0.041；β=-0.204，95%CI=-0.377，-0.031，P=0.021）。
本研究表明，IL-18 和 MCP-1 水平升高与脑白质微观结构损伤有关，而 IL-10 和 IL-2ra 水平升高与 MD 降低有关。
