Gadient R A, Otten U H
California Institute of Technology, Div. Biology, Pasadena 91125, USA.
Prog Neurobiol. 1997 Aug;52(5):379-90. doi: 10.1016/s0301-0082(97)00021-x.
Interleukin-6 (IL-6), a member of the neuropoietic cytokine family, initially was described in terms of its activities in the immune system and during inflammation. Accumulating evidence supports an essential role of IL-6 in the development, differentiation, regeneration and degeneration of neurons in the peripheral and central nervous system. Major sites of IL-6 synthesis are neurons and glial cells. Interleukin-6 functions are mediated by a specific receptor system composed of a binding site and a signal transducer. This receptor system can be modulated by a complex of IL-6 and soluble IL-6 receptor acting as agonist. The IL-6 can exert completely opposite actions on neurons, triggering either neuronal survival after injury or causing neuronal degeneration and cell death in disorders such as Alzheimer's disease. Development of selective IL-6 agonists and antagonists, as well as the usage of soluble IL-6 receptors, offers new possibilities for the treatment of neurodegenerative disorders. Furthermore, optimized genetic mouse models, including transgenic and knockout animals, should help to define the physiological and pathophysiological role of IL-6 in the nervous system.
白细胞介素-6(IL-6)是神经生成性细胞因子家族的一员,最初是根据其在免疫系统和炎症过程中的活性来描述的。越来越多的证据支持IL-6在周围和中枢神经系统神经元的发育、分化、再生和退化中起重要作用。IL-6的主要合成部位是神经元和神经胶质细胞。白细胞介素-6的功能由一个由结合位点和信号转导器组成的特定受体系统介导。该受体系统可被作为激动剂的IL-6和可溶性IL-6受体复合物调节。IL-6可对神经元产生完全相反的作用,在损伤后触发神经元存活,或在诸如阿尔茨海默病等疾病中导致神经元退化和细胞死亡。选择性IL-6激动剂和拮抗剂的开发以及可溶性IL-6受体的使用,为神经退行性疾病的治疗提供了新的可能性。此外,优化的基因小鼠模型,包括转基因和基因敲除动物,应有助于确定IL-6在神经系统中的生理和病理生理作用。