Computational Analysis Supports an Early, Type 17 Cell-Associated Divergence of Blunt Trauma Survival and Mortality.
Computational Analysis Supports an Early, Type 17 Cell-Associated Divergence of Blunt Trauma Survival and Mortality.
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DOI：
10.1097/ccm.0000000000001951
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发表时间：
2016-11
影响因子：
8.8
通讯作者：
Vodovotz Y
中科院分区：
文献类型：
--
作者：
Abboud A;Namas RA;Ramadan M;Mi Q;Almahmoud K;Abdul-Malak O;Azhar N;Zaaqoq A;Namas R;Barclay DA;Yin J;Sperry J;Peitzman A;Zamora R;Simmons RL;Billiar TR;Vodovotz Y
钝性创伤患者可能具有相似的人口学特征和损伤严重程度，但在生存方面有所不同。我们假设这种差异是由于全身炎症的不同轨迹造成的，并利用计算分析来定义这些差异。从493名钝性创伤患者的队列中，我们对存活超过24小时但最终死亡的患者(无幸存者，n=19)和在ICU入院后出院的患者(幸存者，n=19)进行了一项成对的、回顾性的病例对照研究。用计算模型分析在最初的24小时内和超过7天评估的全身炎症介质的数据，以推断炎症的动态网络。创伤/出血的小鼠模型被用来验证来自临床研究的假说。在病人身上没有。中和小鼠抗IL-17A抗体。死亡患者的炎症介质网络密度在7d后随着器官功能障碍评分的增加而增加，提示存在涉及HMGB1、IL-23和Th17途径的早期、自我维持的病理性炎症。幸存者表现出一种与自我分解的模式相称的模式，主要是淋巴反应，包括更高水平的修复性细胞因子IL-22。受到创伤/出血的小鼠在接受抗IL-17A治疗时器官损伤减轻。可变的17型免疫反应是钝性创伤后器官损伤、存活和死亡的标志，并提示基于淋巴样细胞的炎症从自我溶解转变为自我维持的炎症。
Blunt trauma patients may present with similar demographics and injury severity, yet differ with regard to survival. We hypothesized that this divergence was due to different trajectories of systemic inflammation, and utilized computational analyses to define these differences. From a cohort of 493 victims of blunt trauma, we conducted a pairwise, retrospective, case-control study of patients who survived over 24h but ultimately died (non-survivors; n=19) and patients who, following ICU admission, went on to be discharged (survivors; n=19). Data on systemic inflammatory mediators assessed within the first 24h and over 7d were analyzed with computational modeling to infer dynamic networks of inflammation. A mouse model of trauma/hemorrhage was used to verify hypotheses derived from the clinical study. None in patients. Neutralizing anti-IL-17A antibody in mice. Network density among inflammatory mediators in non-survivors increased in parallel with organ dysfunction scores over 7d, suggesting the presence of early, self-sustaining, pathological inflammation involving HMGB1, IL-23, and the Th17 pathway. Survivors demonstrated a pattern commensurate with a self-resolving, predominantly lymphoid response, including higher levels of the reparative cytokine IL-22. Mice subjected to trauma/hemorrhage exhibited reduced organ damage when treated with anti-IL-17A. Variable type 17 immune responses are hallmarks of organ damage, survival, and mortality following blunt trauma, and suggest a lymphoid cell-based switch from self-resolving to self-sustaining inflammation.