Neuroinflammation is increasingly recognized as an important mediator of disease progression in patients with amyotrophic lateral sclerosis (ALS). Recent research suggests that pro-inflammatory microglia in ALS mice promote motoneuron cytotoxicity by secreting reactive oxygen species and pro-inflammatory cytokines. Gene expression analyses indicate that peripheral circulating monocytes from ALS patients are skewed towards a pro-inflammatory state that contributes to ALS disease progression. Better understanding of macrophage phenotypes of ALS patients is therefore warranted. In this study, we demonstrate that M1 macrophages differentiated from ALS circulating monocytes produced more pro-inflammatory cytokines, including IL-6 and TNFα, than M1 macrophages derived from healthy control monocytes. More importantly, IL-6 protein levels of ALS M1 macrophages positively correlated with disease burden, and TNFα protein levels of ALS M1 macrophages positively correlate with disease progression rates. Collectively, these data suggest that monocytes from ALS patients are more readily activated and differentiated to a pro-inflammatory M1 phenotype, and represent a potential target for immunomodulatory therapy.

中文翻译：

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ALS患者单核细胞的激活能力增强。

神经炎症被越来越多地认为是肌萎缩性侧索硬化症（ALS）患者疾病进展的重要介质。最近的研究表明，ALS小鼠中的促炎性小胶质细胞通过分泌活性氧和促炎性细胞因子来促进运动神经元细胞毒性。基因表达分析表明，来自ALS患者的外周循环单核细胞偏向促炎状态，这有助于ALS疾病的发展。因此，需要更好地了解ALS患者的巨噬细胞表型。在这项研究中，我们证明了从ALS循环单核细胞分化出来的M1巨噬细胞比健康对照单核细胞产生的M1巨噬细胞产生更多的促炎性细胞因子，包括IL-6和TNFα。更重要的是，ALS M1巨噬细胞的IL-6蛋白水平与疾病负担呈正相关，而ALS M1巨噬细胞的TNFα蛋白水平与疾病进展率呈正相关。总体而言，这些数据表明，来自ALS患者的单核细胞更容易被激活并分化为促炎性M1表型，并代表了免疫调节疗法的潜在靶标。