Woiciechowsky Christian, Schöning Britta, Stoltenburg-Didinger Gisela, Stockhammer Florian, Volk Hans-Dieter
Klinik für Neurochirurgie, Charité, Campus Virchow-Klinikum, Universitätsmedizin Berlin, D-13353 Berlin, Germany.
Med Sci Monit. 2004 Sep;10(9):BR325-30. Epub 2004 Aug 20.
Gliosis is a characteristic pathology in many central nervous system (CNS) diseases. Cytokines are considered to be effectors of gliosis. It has been shown that pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6 boost glia scar formation. On the other hand, anti-inflammatory cytokines, such as IL-10 and IL-1 receptor antagonist (ra), can act neuroprotectively. Furthermore, various immune mediators and neurotransmitters can modulate the onset of gliosis.
MATERIAL/METHODS: We used 100 male Sprague-Dawley rats to investigate the mechanisms of brain-cytokine-induced astrogliosis using an in vivo model of convection-enhanced delivery of cytokines (IL-beta, IL-6, tumor necrosis factor (TNF)-alpha) into the cerebro-ventricular system. The protective effects of the anti-inflammatory cytokine IL-10 and the neurotransmitter propranolol were also investigated.
With this paradigm, we could clearly demonstrate that IL-6 is a key cytokine mediating astrogliosis, noticeable in the increased expression of glial fibrillary acidic protein (GFAP). Thus intra-cerebroventricular infusion of IL-6 increased GFAP expression in a dose-dependent manner. Furthermore, GFAP expression was also increased by IL-beta, which correspondingly triggered an IL-6 release into the CSF. Accordingly, TNF-alpha, which did not induce IL-6 release, also did not induce gliosis. On the other hand, substances which decrease IL-beta-induced IL-6 production, such as propranolol and IL-10, also dramatically decreased IL-beta triggered gliosis.
IL-6 infusion, as well as IL-beta-induced IL-6 release into the CSF, increase GFAP expression in the cerebral cortex and hippocampus. Accordingly, blockade of the IL-beta-induced IL-6 release by IL-10 and propranolol decreases GFAP expression.
胶质增生是许多中枢神经系统（CNS）疾病的特征性病理表现。细胞因子被认为是胶质增生的效应物。研究表明，白细胞介素（IL）-1和IL-6等促炎细胞因子可促进胶质瘢痕形成。另一方面，抗炎细胞因子，如IL-10和IL-1受体拮抗剂（ra），可发挥神经保护作用。此外，各种免疫介质和神经递质可调节胶质增生的发生。
材料/方法：我们使用100只雄性Sprague-Dawley大鼠，通过将细胞因子（IL-β、IL-6、肿瘤坏死因子（TNF）-α）经对流增强递送进入脑室系统的体内模型，研究脑源性细胞因子诱导星形胶质细胞增生的机制。还研究了抗炎细胞因子IL-10和神经递质普萘洛尔的保护作用。
采用这种模式，我们可以清楚地证明IL-6是介导星形胶质细胞增生的关键细胞因子，在胶质纤维酸性蛋白（GFAP）表达增加中表现明显。因此，脑室内注入IL-6可使GFAP表达呈剂量依赖性增加。此外，IL-β也可增加GFAP表达，相应地引发IL-6释放到脑脊液中。因此，不诱导IL-6释放的TNF-α也不诱导胶质增生。另一方面，降低IL-β诱导的IL-6产生的物质，如普萘洛尔和IL-10，也显著降低IL-β引发的胶质增生。
注入IL-6以及IL-β诱导的IL-6释放到脑脊液中，可增加大脑皮质和海马体中GFAP的表达。因此，IL-10和普萘洛尔阻断IL-β诱导的IL-6释放可降低GFAP表达。
