Inflammatory cytokine cascade released by leukocytes in cerebrospinal fluid after subarachnoid hemorrhage
Inflammatory cytokine cascade released by leukocytes in cerebrospinal fluid after subarachnoid hemorrhage
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DOI：
10.1179/016164101101199243
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发表时间：
2001-10-01
影响因子：
1.9
通讯作者：
Uemura, K
中科院分区：
文献类型：
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作者：
Takizawa, T;Tada, T;Uemura, K
蛛网膜下腔出血（Subarachnoid hemorrhage，SAH）可引起蛛网膜下腔的炎症反应，而炎症反应是由多种细胞因子介导的。为了评估它们在出血后并发症中的作用，我们确定了SAH后脑脊液（CSF）中炎性细胞因子和急性时相蛋白的释放来源和时间过程。采用酶联免疫吸附法（ELISA）检测36例SAH患者脑脊液（CSF）中白细胞介素（IL）-1 β、IL-6、转化生长因子-β 1（TGF-β 1）和C反应蛋白（CRP）水平。SAH后4 ~ 6d，取脑脊液（CSF）中的悬浮细胞，离心后行细胞化学染色，流式细胞仪检测细胞内IL-1 β和IL-6的含量。采用Western blot法检测30例患者脑脊液中TGF-β 1的分子量。脑室腹腔分流术组（n = 19）TGF-β 1水平显著高于非分流组（n = 16）。VP分流组CRP水平明显高于非分流组。IL-6浓度在0-1天内达到最大，由中性粒细胞和单核细胞分泌。ELISA显示IL-1 β的水平始终较低，而流式细胞术分析显示一定比例的单核细胞和淋巴细胞为IL-1 β阳性。根据ELISA，TGF-β 1水平也在第0-1天达到最大值，尽管它往往是来自血小板的无活性形式。SAH后至少13天可检测到TGF-1的25 kDa条带，其可能部分由中性粒细胞和单核细胞分泌。CSF中的CRP水平在第2-3天达到峰值。目前的结果表明，由SAH诱导的白细胞通过释放IL-6和TGF-β 1在蛛网膜下腔出血后炎症中发挥重要作用。CSF中CRP和TGF-β 1水平与SAH后交通性脑积水密切相关。
Subarachnoid hemorrhage (SAH) elicits an inflammatory response in the subarachnoid space, which is mediated by the release of various cytokines. To assess their involvement in post-hemorrhagic complications, we determined the source and time-course of the release of inflammatory cytokines and acute-phase proteins in cerebrospinal fluid (CSF) following SAH. Concentrations of interleukin (IL)-1 beta, IL-6, transforming growth factor-beta1 (TGF-beta1) and C-reactive protein (CRP) in CSF of 36 patients with SAH were measured by enzyme-linked immunoabsorbent assay (ELISA). Floating cells collected from the CSF were centrifuged four to six days after SAH, and examined immunohistochemically, Intracellular IL-1 beta and IL-6 were examined by flow cytometric analysis. The molecular weight of TGF-beta1 in CSF of 30 patients was examined by Western blot analysis. The TGF-beta1 levels of patients who had undergone ventriculoperitoneal (VP) shunt (n = 19) was significantly higher than nonshunt group (n = 16). The CRP levels of VP shunt group was significantly higher than nonshunt group. IL-6 concentration was maximal within day 0-1 and it was secreted by neutrophils and monocytes. ELISA showed consistently low levels of IL-1 beta, whereas a proportion of monocytes and lymphcytes were IL-1 beta -positive by flow cytometric analysis. TGF-beta1 levels were also maximal on day 0-1 according to ELISA, although it tended to be in the inactive form derived from platelets. A 25 kDa band of TGF-1 was detectable for at least 13 days after SAH, which may have been secreted in part by neutrophils and monocytes. CRP levels in CSF peaked on day 2-3. The present results suggest that leukocytes induced by SAH play an important role in post-hemorrhagic inflammation in the subarachnoid space by releasing IL-6 and TGF-beta1. The CRP and TGF-beta1 levels in CSF are strongly concerned with communicating hydrocephalus after SAH.