Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark.
J Cereb Blood Flow Metab. 2012 Sep;32(9):1677-98. doi: 10.1038/jcbfm.2012.88. Epub 2012 Jun 27.
Inflammation is a hallmark of stroke pathology. The cytokines, tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, modulate tissue injury in experimental stroke and are therefore potential targets in future stroke therapy. The effect of these cytokines on infarct evolution depends on their availability in the ischemic penumbra in the early phase after stroke onset, corresponding to the therapeutic window (<4.5 hours), which is similar in human and experimental stroke. This review summarizes a large body of literature on the spatiotemporal and cellular production of TNF, IL-1, and IL-6, focusing on the early phase in experimental and human stroke. We also review studies of cytokines in blood and cerebrospinal fluid in stroke. Tumor necrosis factor and IL-1 are upregulated early in peri-infarct microglia. Newer literature suggests that IL-6 is produced by microglia, in addition to neurons. Tumor necrosis factor- and IL-1-producing macrophages infiltrate the infarct and peri-infarct with a delay. This information is discussed in the context of suggestions that neuronal sensitivity to ischemia may be modulated by cytokines. The fact that TNF and IL-1, and suppossedly also IL-6, are produced by microglia within the therapeutic window place these cells centrally in potential future stroke therapy.
炎症是中风病理的一个标志。细胞因子，肿瘤坏死因子 (TNF)、白细胞介素 (IL)-1 和 IL-6，调节实验性中风中的组织损伤，因此是未来中风治疗的潜在靶点。这些细胞因子对梗死演变的影响取决于它们在中风发作后早期缺血半影区（对应于治疗窗口，<4.5 小时）中的可用性，在人类和实验性中风中，该治疗窗口相似。这篇综述总结了大量关于 TNF、IL-1 和 IL-6 在时空和细胞水平上产生的文献，重点关注实验性和人类中风的早期阶段。我们还回顾了中风患者血液和脑脊液中细胞因子的研究。TNF 和 IL-1 在梗死周围的小胶质细胞中早期上调。新的文献表明，IL-6 除了神经元之外，还由小胶质细胞产生。TNF 和 IL-1 产生的巨噬细胞延迟浸润梗死和梗死周围区。在讨论神经元对缺血的敏感性可能被细胞因子调节的情况下，这一信息是相关的。事实上，TNF 和 IL-1，以及推测的 IL-6，都是在治疗窗口内由小胶质细胞产生的，这使得这些细胞在未来的中风治疗中处于核心地位。
