Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats
Systemically administered interleukin-10 reduces tumor necrosis factor-alpha production and significantly improves functional recovery following traumatic spinal cord injury in rats
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DOI：
10.1089/neu.1999.16.851
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发表时间：
1999-10-01
影响因子：
4.2
通讯作者：
Dietrich, WD
中科院分区：
文献类型：
--
作者：
Bethea, JR;Nagashima, H;Dietrich, WD
在这些研究中，我们研究了脊髓损伤（SCI）后强效细胞因子白细胞介素-10（IL-10）的神经保护作用。通过行为学和形态学终点评估神经保护作用。我们假设损伤诱导的炎症导致神经病理学和随后的功能丧失。因此，通过减轻损伤引起的炎症，我们应该促进功能恢复。纽约大学的装置被用于诱导中度SCI，并研究所产生的炎症反应和抑制这种反应在大鼠中的功能后果。我们确定，SCI诱导肿瘤坏死因子-α（TNF-α）的表达在脊髓和SCI激活的单核细胞从外周循环中分离。在损伤后30分钟给予IL-10（5.0 μ g）显著降低脊髓中和体外SCI激活的单核细胞的TNF-α蛋白的表达。接下来，我们研究了IL-10是否会改善SCI后的功能恢复。随机、双盲研究表明，单次注射IL-10显著改善了损伤后2个月的后肢运动功能，如通过Basso、Beattie和Bresnahan（BBB）旷场行为测试所确定的。IL-10处理的动物的平均BBB评分为18.0 +/-0.5（SEM，n = 9），而盐水处理的对照组的评分为12.9 +/-0.6（SEM，n = 9）。形态学分析表明，IL-10在损伤后2个月使病变体积减少约49%。这些数据表明，急性施用IL-10减少了脊髓中和活化的巨噬细胞的TNF-α合成，具有神经保护作用，并促进SCI后的功能恢复。
In these studies, we examined the neuroprotective effects of the potent antiinflammatory cytokine interleukin-10 (IL-10) following spinal cord injury (SCI). Neuroprotection was assessed by using behavioral and morphological end points. We hypothesized that injury-induced inflammation contributes to the resulting neuropathology and subsequent loss of function. Therefore, by attenuating injury-induced inflammation, we should promote functional recovery. The New York University device was used to induce moderate SCI and study the resulting inflammatory response and functional consequences of inhibiting this response in rats. We determined that SCI induces the expression of tumor necrosis factor-alpha (TNF-alpha) in the spinal cord and by SCI-activated monocytes isolated from the peripheral circulation. IL-10 (5.0 mu g) administered 30 minutes after-injury significantly reduced the expression of TNF-alpha protein in the spinal cord and in vitro by SCI-activated monocytes. Next, we investigated whether IL-10 would improve functional recovery after SCI. Randomized, double-blinded studies demonstrated that a single injection of IL-10 significantly improves hind limb motor function 2 months after injury, as determined by the Basso, Beattie and Bresnahan (BBB) open-field behavioral test. IL-10-treated animals had a mean BBB score of 18.0 +/- 0.5 (SEM, n = 9) compared with a score of 12.9 +/- 0.6 (SEM, n = 9) for the saline-treated controls. Morphological analysis demonstrated that IL-10 reduces lesion volume by approximately 49% 2 months after injury. These data suggest that acute administration of IL-10 reduces TNF-alpha synthesis in the spinal cord and by activated macrophages, is neuroprotective, and promotes functional recovery following SCI.