1Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, PA. 2Department of Surgery, University of Pittsburgh, Pittsburgh, PA. 3Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA. 4Department of Sports Medicine and Nutrition, University of Pittsburgh, Pittsburgh, PA. 5Department of Rehabilitation Science and Technology, University of Pittsburgh, Pittsburgh, PA. 6Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA.
Crit Care Med. 2014 Jun;42(6):1487-97. doi: 10.1097/CCM.0000000000000248.
Blunt trauma and traumatic spinal cord injury induce systemic inflammation that contributes to morbidity. Dysregulated neural control of systemic inflammation postinjury is likely exaggerated in patients with traumatic spinal cord injury. We used in silico methods to discern dynamic inflammatory networks that could distinguish systemic inflammation in traumatic spinal cord injury from blunt trauma.
Retrospective study.
Tertiary care institution.
Twenty-one severely injured thoracocervical traumatic spinal cord injury patients and matched 21 severely injured blunt trauma patients without spinal cord injury.
None.
Serial blood samples were obtained from days 1 to 14 postinjury. Twenty-four plasma inflammatory mediators were quantified. Statistical significance between the two groups was determined by two-way analysis of variance. Dynamic Bayesian network inference was used to suggest dynamic connectivity and central inflammatory mediators. Circulating interleukin-10 was significantly elevated in thoracocervical traumatic spinal cord injury group versus non-spinal cord injury group, whereas interleukin-1β, soluble interleukin-2 receptor-α, interleukin-4, interleukin-5, interleukin-7, interleukin-13, interleukin-17, macrophage inflammatory protein 1α and 1β, granulocyte-macrophage colony-stimulating factor, and interferon-γ were significantly reduced in traumatic spinal cord injury group versus non-spinal cord injury group. Dynamic Bayesian network suggested that post-spinal cord injury interleukin-10 is driven by inducible protein-10, whereas monocyte chemotactic protein-1 was central in non-spinal cord injury dynamic networks. In a separate validation cohorts of 356 patients without spinal cord injury and 85 traumatic spinal cord injury patients, individuals with plasma inducible protein-10 levels more than or equal to 730 pg/mL had significantly prolonged hospital and ICU stay and days on mechanical ventilator versus patients with plasma inducible protein-10 level less than 730 pg/mL.
This is the first study to compare the dynamic systemic inflammatory responses of traumatic spinal cord injury patients versus patients without spinal cord injury, suggesting a key role for inducible protein-10 in driving systemic interleukin-10 and morbidity and highlighting the potential utility of in silico tools to identify key inflammatory drivers.
钝性创伤和外伤性脊髓损伤会引发全身炎症，从而导致发病率升高。受伤后，全身炎症的神经调节失控在创伤性脊髓损伤患者中可能更为严重。我们使用计算方法来辨别能够区分创伤性脊髓损伤和钝性创伤的全身炎症的动态炎症网络。
回顾性研究。
三级保健机构。
21 例严重胸颈段创伤性脊髓损伤患者和 21 例严重钝性创伤但无脊髓损伤的匹配患者。
无。
从损伤后第 1 天至第 14 天连续采集血样。定量检测 24 种血浆炎症介质。通过双向方差分析确定两组间的统计学意义。动态贝叶斯网络推断用于提示动态连接和中心炎症介质。与非脊髓损伤组相比，胸颈段创伤性脊髓损伤组患者的循环白细胞介素-10 显著升高，而白细胞介素-1β、可溶性白细胞介素-2 受体-α、白细胞介素-4、白细胞介素-5、白细胞介素-7、白细胞介素-13、白细胞介素-17、巨噬细胞炎性蛋白-1α 和 1β、粒细胞-巨噬细胞集落刺激因子和干扰素-γ在创伤性脊髓损伤组中显著降低。动态贝叶斯网络提示，脊髓损伤后白细胞介素-10 由诱导蛋白-10 驱动，而单核细胞趋化蛋白-1 在非脊髓损伤的动态网络中起中心作用。在另外一个由 356 例无脊髓损伤和 85 例创伤性脊髓损伤患者组成的验证队列中，与诱导蛋白-10 水平小于或等于 730pg/ml 的患者相比，诱导蛋白-10 水平大于或等于 730pg/ml 的患者的住院时间、ICU 入住时间和机械通气时间明显延长。
这是第一项比较创伤性脊髓损伤患者与无脊髓损伤患者的全身炎症反应的研究，提示诱导蛋白-10 在驱动全身白细胞介素-10 和发病率方面发挥关键作用，并突出了计算工具在识别关键炎症驱动因素方面的潜在效用。
