Bowman George, Dixit Sanat, Bonneau Robert H, Chinchilli Vernon M, Cockroft Kevin M
Division of Neurosurgery, Pennsylvania State University College of Medicine, Milton S Hershey Medical Center, Hershey, Pennsylvania 17033, USA.
Neurosurgery. 2004 Mar;54(3):719-25; discussion 725-6. doi: 10.1227/01.neu.0000108981.73153.6e.
The degree to which inflammation contributes to the development of posthemorrhagic vasospasm is controversial. In the present study, we investigated the relationship between various inflammatory cytokines (tumor necrosis factor-alpha, interleukin [IL]-1alpha, IL-1beta, and IL-6) and the development of experimental vasospasm.
Posthemorrhagic vasospasm was produced in the rat femoral artery model. A latex pouch was placed around each femoral artery, and one pouch was injected with autologous blood and the other with saline as an internal control. Animals were killed at various time points (1 h to 16 d) after surgery (blood exposure), and the degree of vasospasm was assessed by image analysis of artery cross sectional area. Levels of inflammatory cytokines were determined by enzyme-linked immunosorbent assay, and the ability of a polyclonal antibody against rat IL-6 to inhibit vasospasm was tested.
The rat femoral artery model produced a biphasic vasospasm response, with maximal chronic delayed vasospasm occurring at 8 days after hemorrhage. Enzyme-linked immunosorbent assay revealed a significant increase in IL-6 concentrations in blood-exposed arteries relative to saline-exposed arteries at multiple time points (6, 12, 24, and 48 h) after hemorrhage (P < 0.0001). A relative increase in IL-1alpha levels was noted at 24 hours (P < 0.01). IL-1beta levels were similarly elevated in both blood- and saline-exposed arteries, and tumor necrosis factor-alpha levels were not detectable. Administration of a neutralizing polyclonal antibody against rat IL-6 directly into the blood-exposed periarterial pouch at the time of initial surgery resulted in a dose-dependent reduction in the degree of vasospasm compared with vehicle-treated controls at 8 days after hemorrhage (P < 0.05).
These results indicate that cytokine-mediated inflammation is active in the setting of posthemorrhagic vasospasm produced by the rat femoral artery model. In particular, the profound increase in IL-6 levels after exposure to hemorrhage and the ability of a polyclonal antibody against IL-6 to reduce vasospasm suggest that IL-6 may play a prominent role in the development of vasospasm in this model.
炎症在出血后血管痉挛发展过程中所起的作用程度存在争议。在本研究中，我们调查了多种炎性细胞因子（肿瘤坏死因子-α、白细胞介素[IL]-1α、IL-1β和IL-6）与实验性血管痉挛发展之间的关系。
在大鼠股动脉模型中诱导出血后血管痉挛。在每条股动脉周围放置一个乳胶袋，一个袋子注入自体血，另一个注入生理盐水作为内部对照。在手术（血液暴露）后的不同时间点（1小时至16天）处死动物，通过动脉横截面积的图像分析评估血管痉挛程度。采用酶联免疫吸附测定法测定炎性细胞因子水平，并测试抗大鼠IL-6多克隆抗体抑制血管痉挛的能力。
大鼠股动脉模型产生双相血管痉挛反应，出血后8天出现最大程度的慢性延迟性血管痉挛。酶联免疫吸附测定显示，与生理盐水暴露的动脉相比，出血后多个时间点（6、12、24和四十八小时）血液暴露的动脉中IL-6浓度显著升高（P<0.0001）。24小时时IL-1α水平相对升高（P<0.01）。血液暴露和生理盐水暴露的动脉中IL-1β水平均同样升高，且未检测到肿瘤坏死因子-α水平。在初次手术时将抗大鼠IL-6的中和多克隆抗体直接注入血液暴露的动脉周围袋中，与出血后8天的载体处理对照组相比，血管痉挛程度呈剂量依赖性降低（P<0.05）。
这些结果表明，细胞因子介导的炎症在大鼠股动脉模型产生的出血后血管痉挛环境中是活跃的。特别是，出血后IL-6水平的显著升高以及抗IL-6多克隆抗体降低血管痉挛的能力表明，IL-6可能在该模型的血管痉挛发展中起重要作用。
