Yang Jing, Li Wenyi, Tian Mei, Zhang Lei, Du Fengping, Li Xin, Liu Qi, Li Rui, Li Zhenzhong, Dong Hui, Liu Yaling
Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China.
The Key Laboratory of Neurology (Hebei Medical University), Ministry of Education, Shijiazhuang, Hebei, China.
Front Neurosci. 2025 Jan 7;18:1514554. doi: 10.3389/fnins.2024.1514554. eCollection 2024.
Amyotrophic lateral sclerosis (ALS) is a rare, devastating neurodegenerative disease that affects upper and lower motor neurons, resulting in muscle atrophy, spasticity, hyperreflexia, and paralysis. Inflammation plays an important role in the development of ALS, and associated with rapid disease progression. Current observational studies indicate the thinning of cortical thickness in patients with ALS is associated with rapid disease progression and cognitive changes. However, the effects of inflammatory cytokines on cortical thickness in patients with ALS are unclear. Here, we investigated the relationship between inflammatory cytokines and cortical thickness in patients with ALS.
We evaluated 51 patients with ALS for inflammatory cytokines including interleukin (IL)-4, interferon (IFN)-α, IL-1β, IL-2, IL-5, IL-12, tumor necrosis factor (TNF)-α, IL-6, IL-10, IL-8, IL-17, and IFN-γ and analyzed the correlation between these indicators and the ALS functional rating scale-revised (ALSFRS-R) score or disease progression rate (ΔFS score). Twenty-six patients with ALS and 26 controls were studied using whole-cortex analysis, and analyses were performed to examine the correlation between brain cortical thickness and ALSFRS-R or ΔFS scores.
IL-4, IFN-α, IL-1β, and IL-2 levels were significantly correlated with ALSFRS-R scores, and the IL-2 level was significantly correlated with ΔFS scores. After controlling for age and sex, the ALS group had thinner cortexes in multiple clusters across the brain than the control group. Further analyses revealed that cortical thickness in the right superior temporal and lingual gyrus regions was inversely correlated with ΔFS scores. There was a significant positive correlation between the clusters in the right lingual cortex and IL-2 level.
These results suggest cortical thickness was reduced in patients with ALS in motor and non-motor cortical areas. Inflammatory factors (especially IL-2) were correlated with cortical thickness, and both were related to the disease progression rate, suggesting IL-2 plays an important role in ALS.
肌萎缩侧索硬化症（ALS）是一种罕见的、毁灭性的神经退行性疾病，会影响上下运动神经元，导致肌肉萎缩、痉挛、反射亢进和瘫痪。炎症在ALS的发展中起重要作用，并与疾病的快速进展相关。目前的观察性研究表明，ALS患者的皮质厚度变薄与疾病的快速进展和认知变化有关。然而，炎症细胞因子对ALS患者皮质厚度的影响尚不清楚。在此，我们研究了ALS患者炎症细胞因子与皮质厚度之间的关系。
我们评估了51例ALS患者的炎症细胞因子，包括白细胞介素（IL）-4、干扰素（IFN）-α、IL-1β、IL-2、IL-5、IL-12、肿瘤坏死因子（TNF）-α、IL-6、IL-10、IL-8、IL-17和IFN-γ，并分析了这些指标与ALS功能评定量表修订版（ALSFRS-R）评分或疾病进展率（ΔFS评分）之间的相关性。对26例ALS患者和26例对照进行全皮质分析，并进行分析以检查脑皮质厚度与ALSFRS-R或ΔFS评分之间的相关性。
IL-4、IFN-α、IL-1β和IL-2水平与ALSFRS-R评分显著相关，IL-2水平与ΔFS评分显著相关。在控制年龄和性别后，ALS组全脑多个脑区的皮质比对照组更薄。进一步分析显示，右侧颞上回和舌回区域的皮质厚度与ΔFS评分呈负相关。右侧舌皮质的脑区与IL-2水平之间存在显著正相关。
这些结果表明，ALS患者运动和非运动皮质区域的皮质厚度均降低。炎症因子（尤其是IL-2）与皮质厚度相关，且两者均与疾病进展率有关，提示IL-2在ALS中起重要作用。
