Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study.
Prehospital immune responses and development of multiple organ dysfunction syndrome following traumatic injury: A prospective cohort study.
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创伤性损伤后，院前免疫反应和多个器官功能障碍综合征的发展：一项前瞻性队列研究。
DOI：
10.1371/journal.pmed.1002338
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发表时间：
2017-07
期刊：
影响因子：
15.8
通讯作者：
Lord JM
中科院分区：
文献类型：
--
作者：
Hazeldine J;Naumann DN;Toman E;Davies D;Bishop JRB;Su Z;Hampson P;Dinsdale RJ;Crombie N;Duggal NA;Harrison P;Belli A;Lord JM
几乎所有调查创伤免疫反应的研究都分析了入院后获得的血液样本。因此，我们对损伤后即刻患者的免疫状态以及这可能如何影响患者预后知之甚少。因此，本研究的目的是全面评估创伤后1小时内的超早期免疫反应，并对其与多器官功能障碍综合征（MODS）发生的关系进行探索性分析。分析了89名成人创伤患者（平均年龄41岁，范围18 - 90岁，75名男性）对创伤的免疫和炎症反应，平均损伤严重程度评分（ISS）为24（范围9 - 66），在损伤1小时内采集血样（平均采样时间42分钟，范围17 - 60分钟）。在创伤的几分钟内，观察到全面的白细胞增多，血清促炎和抗炎细胞因子升高，以及先天性细胞活化的证据，包括中性粒细胞胞外陷阱的产生和单核细胞和中性粒细胞上toll样受体2和CD11b的表面表达升高。还检测到与免疫受损一致的特征，特别是免疫抑制性CD16 BRIGHT CD62 LDIM中性粒细胞数量增加（对照组为82.07 x 106/l ± 18.94，创伤组为1，092 x 106/l ± 165，p <0.0005）和CD14 + HLA-DR低/−单核细胞（对照组34.96 x 106/l ± 4.48 vs创伤组95.72 x 106/l ± 8.0，p <0.05），并降低了白细胞对脂多糖刺激的细胞因子分泌。通过二元逻辑回归的探索性分析发现，绝对自然杀伤T（NKT）细胞数量与随后的MODS发展之间存在潜在关联。研究的局限性包括相对较小的样本量和缺乏与适应性免疫细胞功能相关的数据。我们的研究强调了创伤免疫反应的动态和复杂性，在损伤后1小时内，免疫改变与激活和抑制一致。这些变化，特别是NKT细胞数量的变化与患者结局（如MODS）的关系值得进一步研究。在这项前瞻性队列研究中，Jon Hazeldine及其同事调查了创伤患者在受伤后立即以及受伤后数小时和数天内的免疫和炎症反应。虽然人们认识到创伤性损伤引起了深刻的免疫和炎症反应，但我们的知识几乎完全基于对患者入院后血液样本的分析。关于创伤患者在受伤后的免疫和炎症状态知之甚少，从而限制了我们确定影响患者结局的因素、治疗分层和开发新疗法的能力。这项研究的目的是提供有关创伤后几分钟内发生的超早期免疫和炎症反应的信息。我们分析了89例成人创伤患者伤后1小时内以及伤后4 - 12和48 - 72小时外周血中免疫细胞的组成和功能以及细胞因子的浓度。我们发现创伤性损伤导致立即免疫功能障碍，伴随的免疫激活和抑制的证据在受伤后几分钟内检测到。我们的工作揭示了创伤后早期免疫反应的动态性质，揭示了在受伤后几分钟内获得的血液样本中检测到的某些特征在创伤后数小时和数天内获得的后续样本中不存在。免疫细胞活化和抑制性细胞的产生发生在损伤后几分钟内，支持创伤后立即伴随诱导免疫活化和抑制的概念。对损伤的急性免疫应答的复杂性质表明，靶向免疫应答的1个要素不太可能减少免疫轻瘫或多器官功能障碍综合征（MODS）的发生率。
Almost all studies that have investigated the immune response to trauma have analysed blood samples acquired post-hospital admission. Thus, we know little of the immune status of patients in the immediate postinjury phase and how this might influence patient outcomes. The objective of this study was therefore to comprehensively assess the ultra-early, within 1-hour, immune response to trauma and perform an exploratory analysis of its relationship with the development of multiple organ dysfunction syndrome (MODS). The immune and inflammatory response to trauma was analysed in 89 adult trauma patients (mean age 41 years, range 18–90 years, 75 males) with a mean injury severity score (ISS) of 24 (range 9–66), from whom blood samples were acquired within 1 hour of injury (mean time to sample 42 minutes, range 17–60 minutes). Within minutes of trauma, a comprehensive leukocytosis, elevated serum pro- and anti-inflammatory cytokines, and evidence of innate cell activation that included neutrophil extracellular trap generation and elevated surface expression of toll-like receptor 2 and CD11b on monocytes and neutrophils, respectively, were observed. Features consistent with immune compromise were also detected, notably elevated numbers of immune suppressive CD16BRIGHT CD62LDIM neutrophils (82.07 x 106/l ± 18.94 control versus 1,092 x 106/l ± 165 trauma, p < 0.0005) and CD14+HLA-DRlow/− monocytes (34.96 x 106/l ± 4.48 control versus 95.72 x 106/l ± 8.0 trauma, p < 0.05) and reduced leukocyte cytokine secretion in response to lipopolysaccharide stimulation. Exploratory analysis via binary logistic regression found a potential association between absolute natural killer T (NKT) cell numbers and the subsequent development of MODS. Study limitations include the relatively small sample size and the absence of data relating to adaptive immune cell function. Our study highlighted the dynamic and complex nature of the immune response to trauma, with immune alterations consistent with both activation and suppression evident within 1 hour of injury. The relationship of these changes, especially in NKT cell numbers, to patient outcomes such as MODS warrants further investigation. In this prospective cohort study, Jon Hazeldine and colleagues investigate the immune and inflammatory response of trauma patients immediately after and in the hours and days following injury. Whilst it is recognised that traumatic injury elicits a profound immune and inflammatory response, our knowledge is based almost entirely upon the analysis of blood samples acquired from patients post-hospital admission. Very little is known with regards to the immune and inflammatory status of trauma patients in the immediate aftermath of injury, thereby limiting our ability to determine factors influencing patient outcome, stratification for treatment, and the development of novel therapeutics. This study was undertaken to provide information on the ultra-early immune and inflammatory response that occurs within minutes of traumatic injury. We analysed the composition and function of immune cells and the concentrations of cytokines in peripheral blood samples acquired from 89 adult trauma patients within 1 hour of injury as well as 4–12 and 48–72 hours postinjury. We found traumatic injury resulted in immediate immune dysfunction, with evidence of concomitant immune activation and suppression detected within minutes of injury. Our work uncovered a dynamic nature to the very early post-trauma immune response, revealing that certain features detected in blood samples acquired within minutes of injury were absent from subsequent samples obtained in the hours and days post-trauma. Immune cell activation and the generation of inhibitory cells occur within minutes of injury, supporting the notion of a concomitant induction of immune activation and suppression immediately after trauma. The complex nature of the acute immune response to injury suggests that targeting 1 element of the immune response is unlikely to reduce immuneparesis or the incidence of multiple organ dysfunction syndrome (MODS).
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影响因子：
3.7
作者：
Hirose T;Hamaguchi S;Matsumoto N;Irisawa T;Seki M;Tasaki O;Hosotsubo H;Yamamoto N;Yamamoto K;Akeda Y;Oishi K;Tomono K;Shimazu T
通讯作者：
Shimazu T
影响因子：
4.4
作者：
Aneja, Rajesh;Odoms, Kelli;Wong, Hector R.
通讯作者：
Wong, Hector R.
影响因子：
1.9
作者：
Brasiliano Ferreira, Luiz Carlos;Regner, Andrea;Simon, Daniel
通讯作者：
Simon, Daniel
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y
影响因子：
3.7
作者：
Liao Y;Liu P;Guo F;Zhang ZY;Zhang Z
通讯作者：
Zhang Z