Hazeldine Jon, Naumann David N, Toman Emma, Davies David, Bishop Jonathan R B, Su Zhangjie, Hampson Peter, Dinsdale Robert J, Crombie Nicholas, Duggal Niharika Arora, Harrison Paul, Belli Antonio, Lord Janet M
Institute of Inflammation and Ageing, University of Birmingham, Birmingham, United Kingdom.
NIHR Surgical Reconstruction and Microbiology Research Centre, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.
PLoS Med. 2017 Jul 18;14(7):e1002338. doi: 10.1371/journal.pmed.1002338. eCollection 2017 Jul.
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.
几乎所有研究创伤免疫反应的研究都分析了入院后采集的血样。因此,我们对患者在受伤后即刻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)发生发展的关系进行探索性分析。
对89例成年创伤患者(平均年龄41岁,范围18 - 90岁,75例男性)的免疫和炎症反应进行分析,这些患者的平均损伤严重程度评分(ISS)为24(范围9 - 66),在受伤后1小时内采集血样(平均采样时间42分钟,范围17 - 60分钟)。在创伤后数分钟内,观察到全面的白细胞增多、血清促炎和抗炎细胞因子升高,以及固有细胞活化的证据,包括中性粒细胞胞外陷阱的产生以及单核细胞和中性粒细胞上分别的Toll样受体2和CD11b表面表达升高。还检测到与免疫功能受损一致的特征,特别是免疫抑制性CD16BRIGHT CD62LDIM中性粒细胞数量增加(对照组82.07×10⁶/l±18.94,创伤组1,092×10⁶/l±165,p<0.0005)和CD14+HLA - DRlow/-单核细胞数量增加(对照组34.96×10⁶/l±4.48,创伤组95.72×10⁶/l±8.0,p<0.05),以及脂多糖刺激后白细胞细胞因子分泌减少。通过二元逻辑回归进行的探索性分析发现绝对自然杀伤T(NKT)细胞数量与随后发生的MODS之间存在潜在关联。研究局限性包括样本量相对较小以及缺乏与适应性免疫细胞功能相关的数据。
我们的研究突出了创伤免疫反应的动态和复杂性,在受伤后1小时内明显存在与激活和抑制一致的免疫改变。这些变化,尤其是NKT细胞数量的变化,与MODS等患者预后的关系值得进一步研究。