Kerkis Irina, da Silva Álvaro Prieto, Araldi Rodrigo Pinheiro
Genetics Laboratory, Center of Development and Innovation, Butantan Institute, São Paulo, Brazil.
BioDecision Analytics Ltda., São Paulo, Brazil.
Front Immunol. 2024 Jun 24;15:1400533. doi: 10.3389/fimmu.2024.1400533. eCollection 2024.
Interleukin-6 (IL-6) is a versatile cytokine crucial for immune response modulation, inflammation regulation, and various physiological processes in the body. Its wide-ranging functions underscore its importance in maintaining health. Dysregulated IL-6 is closely associated with many diseases, making it a key research and therapeutic target. Elevated IL-6 levels in the central nervous system worsen neuroinflammation in neurodegenerative diseases by activating microglia and astrocytes and releasing pro-inflammatory cytokines and neurotoxic molecules. Moreover, dysregulated IL-6 weakens the blood-brain barrier, exacerbating neuroinflammation and neuronal damage by allowing peripheral immune cells and inflammatory mediators to enter the brain. Mesenchymal stem cells (MSCs) show promise in modulating neuroinflammation by regulating IL-6 levels. They effectively suppress pro-inflammatory cytokines, including IL-6, while promoting anti-inflammatory factors. This therapeutic approach highlights the importance of targeting IL-6 and other inflammatory mediators to alleviate neuroinflammation and its adverse effects on neurological disorders. This review provides a comprehensive overview of IL-6's involvement in neurological disorders, examining endogenous IL-6 and IL-6 derived from MSCs. We explore IL-6's mechanisms affecting neuronal function, survival, and immune modulation in the central nervous system. Additionally, we discuss the potential of MSC-derived IL-6 in neuroregeneration and neuroprotection. By elucidating IL-6's interplay with neurological pathologies, this review offers insights into novel therapeutic strategies targeting IL-6 signaling pathways for neurological disorders.
白细胞介素-6(IL-6)是一种多功能细胞因子,对免疫反应调节、炎症调控以及身体的各种生理过程至关重要。其广泛的功能突显了它在维持健康方面的重要性。IL-6失调与许多疾病密切相关,使其成为关键的研究和治疗靶点。中枢神经系统中IL-6水平升高会通过激活小胶质细胞和星形胶质细胞并释放促炎细胞因子和神经毒性分子,加重神经退行性疾病中的神经炎症。此外,失调的IL-6会削弱血脑屏障,通过允许外周免疫细胞和炎症介质进入大脑,加剧神经炎症和神经元损伤。间充质干细胞(MSCs)在通过调节IL-6水平来调节神经炎症方面显示出前景。它们能有效抑制包括IL-6在内的促炎细胞因子,同时促进抗炎因子。这种治疗方法突显了靶向IL-6和其他炎症介质以减轻神经炎症及其对神经系统疾病的不良影响的重要性。本综述全面概述了IL-6在神经系统疾病中的作用,研究了内源性IL-6和源自MSCs的IL-6。我们探讨了IL-6影响中枢神经系统中神经元功能、存活和免疫调节的机制。此外,我们还讨论了MSCs衍生的IL-6在神经再生和神经保护方面的潜力。通过阐明IL-6与神经病理学的相互作用,本综述为针对神经系统疾病的IL-6信号通路的新型治疗策略提供了见解。