Tian Mei, Xin Cheng, Huo Jia, Liu Qi, Dong Hui, Bai Lin, Wang Yafei, Li Rui, Liu Yaling
Key Laboratory of Clinical Neurology, Ministry of Education, Hebei Medical University, Shijiazhuang, China.
Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Front Neurol. 2025 Jul 4;16:1605822. doi: 10.3389/fneur.2025.1605822. eCollection 2025.
In amyotrophic lateral sclerosis (ALS), immune cells become activated, resulting in a persistent pro-inflammatory milieu and contributing to the development of ALS. Adiponectin produces anti-inflammatory effects via its adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). Currently, there has been limited research conducted on the correlation between adiponectin and inflammation in ALS.
This cross-sectional study recruited a cohort of 82 ALS patients and 25 controls. Adiponectin and inflammatory mediators in plasma were measured using enzyme-linked immunosorbent assay (ELISA). Furthermore, flow cytometry, immunocytochemistry, and ELISA were employed to examine the levels of AdipoR1, AdipoR2, and inflammatory markers in monocytes and macrophages obtained from ALS patients. The effects of Adiponectin receptor agonists (AdipoRon) on AdipoR expression, inflammatory responses, and macrophages polarization were investigated.
Plasma adiponectin level in ALS patients was markedly lower than controls. This decrease was found to be positively associated with IL-1β, IL-2, IL-6, IL-8, and TNF-α, while negatively correlated with IL-4 and IL-10. Furthermore, there was a positive correlation between plasma adiponectin level and ALS Functional Rating Scale-Revised (ALSFRS-R), and a negative correlation with the disease progression rate (δFS). Mediation research demonstrated that IL-2, or TNF-α, or IL-10 acted as a mediator between adiponectin and δFS. AdipoR1 and AdipoR2 showed a notable increase in expression in peripheral blood monocytes and activated macrophages obtained from ALS patients, concomitant with elevated level of IL-1β. AdipoRon treatment resulted in a decrease in the expression of AdipoR1. Simultaneously, AdipoRon decreased the levels of IL-1β and MHC-II, while boosting the levels of IL-10 and CD206. This regulation enabled the transformation of macrophages from the M1 to the M2 phenotype, therefore aiding in the protection of neurons.
Our findings demonstrated a notable association between adiponectin level and inflammation in the peripheral regions of ALS patients. These results may offer new understanding into the control of inflammation and propose a possible treatment approach for ALS.
在肌萎缩侧索硬化症（ALS）中，免疫细胞被激活，导致持续的促炎环境，并促进ALS的发展。脂联素通过其脂联素受体1（AdipoR1）和脂联素受体2（AdipoR2）产生抗炎作用。目前，关于脂联素与ALS炎症之间的相关性研究有限。
这项横断面研究招募了82例ALS患者和25名对照。使用酶联免疫吸附测定（ELISA）测量血浆中的脂联素和炎症介质。此外，采用流式细胞术、免疫细胞化学和ELISA检测从ALS患者获得的单核细胞和巨噬细胞中AdipoR1、AdipoR2和炎症标志物的水平。研究了脂联素受体激动剂（AdipoRon）对AdipoR表达、炎症反应和巨噬细胞极化的影响。
ALS患者的血浆脂联素水平明显低于对照组。发现这种降低与IL-1β、IL-2、IL-6、IL-8和TNF-α呈正相关，而与IL-4和IL-10呈负相关。此外，血浆脂联素水平与ALS功能评定量表修订版（ALSFRS-R）呈正相关，与疾病进展率（δFS）呈负相关。中介研究表明，IL-2、或TNF-α、或IL-10在脂联素和δFS之间起中介作用。AdipoR1和AdipoR2在从ALS患者获得的外周血单核细胞和活化巨噬细胞中的表达显著增加，同时IL-1β水平升高。AdipoRon治疗导致AdipoR1表达降低。同时，AdipoRon降低了IL-1β和MHC-II的水平，同时提高了IL-10和CD206的水平。这种调节使巨噬细胞从M1表型转变为M2表型，从而有助于保护神经元。
我们的研究结果表明脂联素水平与ALS患者外周区域的炎症之间存在显著关联。这些结果可能为炎症控制提供新的认识，并为ALS提出一种可能的治疗方法。
