Winter Craig D, Pringle Ashley K, Clough Geraldine F, Church Martin K
Neurosurgical Department, Wessex Neurological Centre, Southampton, University Hospitals NHS Trust, School of Medicine, University of Southampton, SO16 7PX, UK.
Brain. 2004 Feb;127(Pt 2):315-20. doi: 10.1093/brain/awh039. Epub 2003 Nov 25.
Previous studies have suggested that an increased production of the pro-inflammatory cytokines interleukin-6 (IL-6) and interleukin-1beta (IL-1beta) can influence patient outcome following a severe head injury. However, these studies have relied upon measurements of cytokine levels in CSF or serum, rather than the brain parenchyma itself. Recently, a method of intracranial microdialysis has been developed which permits the efficient recovery of macromolecules from the parenchyma. We have used this technique to investigate whether there is a correlation between patient outcome and parenchymally derived cytokines. Fourteen patients who were admitted to the Wessex Neurological Centre with severe head injury were selected for the study. This group of patients consisted of seven males and seven females with an age range of 21-77 years. Patients were treated according to standard protocols including emergency craniotomy where necessary. Microdialysis probes were implanted into the frontal region contralateral to the site of the primary injury. Approximately 200 micro l of dialysate was recovered every 8-12 h, and the concentrations of IL-6, IL-1beta and nerve growth factor (NGF) were determined by commercial enzyme-linked immunosorbent assays. Patients were assessed initially using the Glasgow coma score, and survivors were assessed after 6 months using the Glasgow outcome scale. Significantly (P = 0.04) higher levels of IL-6 were found in patients who survived compared with those who died. Also, there was a significant correlation between peak IL-6 levels and Glasgow outcome scores (r(2) = 0.34, P = 0.03, n = 14). The levels of IL-1beta and NGF were similar in both groups of patients. From these data, we suggest that IL-6 is an endogenous neuroprotective cytokine produced in response to severe head trauma.
先前的研究表明,促炎细胞因子白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)产量的增加会影响重度颅脑损伤患者的预后。然而,这些研究依赖于脑脊液或血清中细胞因子水平的测量,而非脑实质本身。最近,一种颅内微透析方法已被开发出来,它能有效地从脑实质中回收大分子物质。我们已使用该技术来研究患者预后与脑实质衍生细胞因子之间是否存在关联。14名因重度颅脑损伤入住韦塞克斯神经中心的患者被选入该研究。这组患者包括7名男性和7名女性,年龄范围为21至77岁。患者按照标准方案进行治疗,必要时包括急诊开颅手术。微透析探针被植入到原发损伤部位对侧的额叶区域。每8至12小时回收约200微升透析液,并通过商业酶联免疫吸附测定法测定IL-6、IL-1β和神经生长因子(NGF)的浓度。最初使用格拉斯哥昏迷评分对患者进行评估,幸存者在6个月后使用格拉斯哥预后量表进行评估。与死亡患者相比,存活患者的IL-6水平显著更高(P = 0.04)。此外,IL-6峰值水平与格拉斯哥预后评分之间存在显著相关性(r² = 0.34,P = 0.03,n = 14)。两组患者的IL-1β和NGF水平相似。根据这些数据,我们认为IL-6是一种内源性神经保护细胞因子,在重度颅脑创伤后产生。