Ching San, He Lingli, Lai Wenmin, Quan Ning
Department of Oral Biology, Ohio State University, Columbus, OH 43210-1094, USA.
Brain Behav Immun. 2005 Mar;19(2):127-37. doi: 10.1016/j.bbi.2004.06.001.
This study investigates the role of type I IL-1 receptor (IL-1R1) in mediating the recruitment of leukocytes into the brain parenchyma in mice. Intracerebroventricular (icv) injection of interleukin IL-1beta induced infiltration of leukocytes between 8 and 72 h after the injection. Leukocytes were rarely found in the brain tissue of saline-injected animals. At 8h after IL-1beta injection, leukocytes were seen lining the blood vessels of the brain and sparsely scattered infiltration of leukocytes was found in the cortex. Peak infiltration of leukocytes, which distributed evenly throughout the brain, was seen at 16 h post-injection. The number of leukocytes in the brain declined thereafter and no leukocytes were found 72 h post-injection. This phenomenon was replicated in mice deficient in lymphotoxin-alpha (LT(alpha)), IL-6, interferon (IFN)-gamma receptor, or the tumor necrosis factor (TNF)-alpha receptor, but abrogated in animals deficient in IL-1R1. ICV injection of IFN-gamma or TNF-alpha, but not IL-6 or IL-12, also induced leukocyte infiltration into the brain. Injection of IL-1beta, IFN-gamma, TNF-alpha, IL-6, and IL-12 induced IL-1beta expression in the brain, with IL-6 and IL-12 being the least effective. Leukocyte infiltration induced by icv IFN-gamma and TNF-alpha was also abrogated in IL-1R1-knockout animals. The induced infiltrating leukocytes were identified as neutrophils. Chronic infection with Trypanosoma brucei resulted in the recruitment of T cells, but no other cell types, into the brain. This did not occur in IL-1R1-knockout mice. Thus, IL-1R1 appears to be important for the recruitment of leukocytes across the blood-brain barrier.
本研究调查了I型白细胞介素-1受体（IL-1R1）在介导小鼠脑实质中白细胞募集过程中的作用。脑室内（icv）注射白细胞介素IL-1β可在注射后8至72小时诱导白细胞浸润。在注射生理盐水的动物脑组织中很少发现白细胞。IL-1β注射后8小时，可见白细胞沿脑血管排列，在皮质中发现有稀疏散在的白细胞浸润。注射后16小时可见白细胞浸润达到峰值，且在整个脑内分布均匀。此后脑内白细胞数量下降，注射后72小时未发现白细胞。这种现象在缺乏淋巴毒素-α（LT(α)）、IL-6、干扰素（IFN）-γ受体或肿瘤坏死因子（TNF）-α受体的小鼠中也有出现，但在缺乏IL-1R1的动物中则未出现。脑室内注射IFN-γ或TNF-α，但不注射IL-6或IL-12，也可诱导白细胞浸润入脑。注射IL-1β、IFN-γ、TNF-α、IL-6和IL-12均可诱导脑内IL-1β表达，其中IL-6和IL-12的作用最不明显。脑室内注射IFN-γ和TNF-α诱导的白细胞浸润在IL-1R1基因敲除动物中也未出现。诱导浸润的白细胞被鉴定为中性粒细胞。布氏锥虫慢性感染导致T细胞募集至脑内，但未发现其他细胞类型。这种情况在IL-1R1基因敲除小鼠中未发生。因此，IL-1R1似乎对白细胞穿越血脑屏障的募集过程很重要。
