Morganti-Kossmann M C, Hans V H, Lenzlinger P M, Dubs R, Ludwig E, Trentz O, Kossmann T
Department of Surgery, University Hospital, Zurich, Switzerland.
J Neurotrauma. 1999 Jul;16(7):617-28. doi: 10.1089/neu.1999.16.617.
Traumatic brain injury (TBI) induces local and systemic immunologic changes, release of cytokines, and cell activation. Perpetuation of these cascades may contribute to secondary damage to the brain. Therefore, the ability of the antiinflammatory mediator transforming growth factor-beta (TGF-beta) to downregulate intrathecal immunoactivation may be of fundamental value for diminishing the incidence and extent of secondary insults. In this study, the release of TGF-beta into cerebrospinal fluid (CSF) and serum of 22 patients with severe TBI was analyzed with respect to the function of the blood-brain barrier (BBB) for 21 days. Levels of TGF-beta in CSF increased to their maximum on the first day (median, 1.26 ng/mL), thereafter decreasing gradually over time. Median TGF-beta values in serum always remained within the reference interval (6.5 to 71.5 ng/mL). Daily assessment of the CSF-serum albumin quotient (QA) and of the CSF-serum TGF-beta quotient (QTGF-beta) showed a strong correlation between maximal QTGF-beta and QA, indicating a passage of this cytokine from the periphery to the intrathecal compartment across the BBB. However, calculation of the TGF-beta index (QTGF-beta/Q(A)) suggested a cerebral production of TGF-beta in 9 of 22 patients. Levels of TGF-beta could not be correlated with extent of initial injury by computed tomography (CT), CD4/CD8 ratios, acute lung injury, or clinical outcome as rated by the Glasgow Outcome Scale (GOS). Although increased levels of TGF-beta in CSF seem to parallel BBB function, a partial intrathecal production is suggested, possibly modulated by elevation of interleukin-6 (IL-6). Thus, TGF-beta may function as a factor in the complex cytokine network following TBI, acting as an antiinflammatory and neuroprotective mediator.
创伤性脑损伤（TBI）会引发局部和全身的免疫变化、细胞因子释放以及细胞活化。这些级联反应的持续存在可能导致大脑的继发性损伤。因此，抗炎介质转化生长因子-β（TGF-β）下调鞘内免疫激活的能力对于降低继发性损伤的发生率和程度可能具有重要价值。在本研究中，对22例重度TBI患者的脑脊液（CSF）和血清中TGF-β的释放情况进行了为期21天的分析，以了解血脑屏障（BBB）的功能。CSF中TGF-β水平在第一天升至最高（中位数为1.26 ng/mL），此后随时间逐渐下降。血清中TGF-β的中位数始终保持在参考区间（6.5至71.5 ng/mL）内。每日评估CSF-血清白蛋白商（QA）和CSF-血清TGF-β商（QTGF-β）显示，最大QTGF-β与QA之间存在强相关性，表明该细胞因子可通过BBB从外周进入鞘内间隙。然而，TGF-β指数（QTGF-β/Q(A)）的计算表明，22例患者中有9例存在大脑TGF-β的产生。TGF-β水平与计算机断层扫描（CT）所示的初始损伤程度、CD4/CD8比值、急性肺损伤或格拉斯哥预后量表（GOS）评定的临床结局均无相关性。尽管CSF中TGF-β水平的升高似乎与BBB功能平行，但提示存在部分鞘内产生，可能受白细胞介素-6（IL-6）升高的调节。因此，TGF-β可能在TBI后的复杂细胞因子网络中发挥作用，作为一种抗炎和神经保护介质。
