Mathiesen T, Edner G, Ulfarsson E, Andersson B
Department of Neurosurgery, Karolinska Hospital, Stockholm, Sweden.
J Neurosurg. 1997 Aug;87(2):215-20. doi: 10.3171/jns.1997.87.2.0215.
Subarachnoid hemorrhage (SAH) causes an inflammatory reaction and may lead to ischemic brain damage. Experimental ischemia has been shown to be connected with the alarm-reaction cytokines interleukin-1 receptor antagonist (IL-1Ra) and tumor necrosis factor-alpha (TNF alpha). Increased levels of these cytokines, however, have not been detected thus far in patients following an SAH event. For this reason daily cerebrospinal fluid (CSF) samples were collected from 22 consecutively enrolled patients with SAH and from 10 non-SAH patients (controls). The CSF samples were studied using immunoassays for IL-1Ra and TNF alpha to investigate whether an SAH caused increased cytokine levels. The mean IL-1Ra levels were significantly higher in patients with SAH who were in poor clinical condition on admission than in those who were in good condition (318 pg/ml vs. 82 pg/ml, p < 0.02). The IL-1Ra levels increased during delayed ischemic episodes and after surgery in patients who were in poor clinical condition. Significant increases in IL-1Ra and TNF alpha were detected during Days 4 through 10 in patients suffering from SAH who eventually had a poor outcome (p < 0.05). Patients with good outcomes and control patients had low levels of these cytokines. The levels of IL-1Ra increased after surgery in patients with Hunt and Hess Grades III through V, but not in those with Grade I or II. This finding indicates that patients in poor clinical condition have a labile biochemical state in the brain that is reflected in increased cytokine levels following the surgical trauma. Both IL-1Ra and TNF alpha are known to induce fever, malaise, leukocytosis, and nitric oxide synthesis and to mediate ischemic and traumatic brain injuries. The present study shows that levels of these cytokines increase after SAH occurs and that high cytokine levels correlate with brain damage. It is therefore likely that fever, leukocytosis, and nitric oxide synthesis are also mediated by IL-1 in patients suffering from SAH and it is probable that the inflammatory mediators contribute to brain damage.
蛛网膜下腔出血（SAH）会引发炎症反应，并可能导致缺血性脑损伤。实验性缺血已被证明与警报反应细胞因子白细胞介素-1受体拮抗剂（IL-1Ra）和肿瘤坏死因子-α（TNFα）有关。然而，迄今为止，在SAH事件后的患者中尚未检测到这些细胞因子水平的升高。因此，连续收集了22例SAH患者和10例非SAH患者（对照组）的每日脑脊液（CSF）样本。使用针对IL-1Ra和TNFα的免疫测定法研究CSF样本，以调查SAH是否会导致细胞因子水平升高。入院时临床状况较差的SAH患者的平均IL-1Ra水平显著高于状况良好的患者（318 pg/ml对82 pg/ml，p < 0.02）。临床状况较差的患者在延迟缺血发作期间和手术后IL-1Ra水平升高。最终预后不良的SAH患者在第4天至第10天期间检测到IL-1Ra和TNFα显著升高（p < 0.05）。预后良好的患者和对照患者的这些细胞因子水平较低。Hunt和Hess分级为III至V级的患者术后IL-1Ra水平升高，而I级或II级患者则未升高。这一发现表明，临床状况较差的患者大脑中的生化状态不稳定，这在手术创伤后细胞因子水平升高中得到体现。已知IL-1Ra和TNFα都会引起发热、不适、白细胞增多和一氧化氮合成，并介导缺血性和创伤性脑损伤。本研究表明，SAH发生后这些细胞因子水平会升高，且高细胞因子水平与脑损伤相关。因此，SAH患者的发热、白细胞增多和一氧化氮合成很可能也由IL-1介导，并且炎症介质很可能导致脑损伤。
