淋巴细胞群体的早期变化与创伤患者多器官功能障碍综合征的发生有关。
Early changes within the lymphocyte population are associated with the development of multiple organ dysfunction syndrome in trauma patients.
作者信息
Manson Joanna, Cole Elaine, De'Ath Henry D, Vulliamy Paul, Meier Ute, Pennington Dan, Brohi Karim
机构信息
Barts Centre for Trauma Sciences, Blizard Institute, QMUL, London, E1 2AT, UK.
Centre for Neuroscience, Blizard Institute, QMUL, London, E1 2AT, UK.
出版信息
Crit Care. 2016 Jun 7;20(1):176. doi: 10.1186/s13054-016-1341-2.
BACKGROUND
Early survival following severe injury has been improved with refined resuscitation strategies. Multiple organ dysfunction syndrome (MODS) is common among this fragile group of patients leading to prolonged hospital stay and late mortality. MODS after trauma is widely attributed to dysregulated inflammation but the precise mechanics of this response and its influence on organ injury are incompletely understood. This study was conducted to investigate the relationship between early lymphocyte responses and the development of MODS during admission.
METHODS
During a 24-month period, trauma patients were recruited from an urban major trauma centre to an ongoing, observational cohort study. Admission blood samples were obtained within 2 h of injury and before in-hospital intervention, including blood transfusion. The study population was predominantly male with a blunt mechanism of injury. Lymphocyte subset populations including T helper, cytotoxic T cells, NK cells and γδ T cells were identified using flow cytometry. Early cytokine release and lymphocyte count during the first 7 days of admission were also examined.
RESULTS
This study demonstrated that trauma patients who developed MODS had an increased population of NK dim cells (MODS vs no MODS: 22 % vs 13 %, p < 0.01) and reduced γδ-low T cells (MODS vs no MODS: 0.02 (0.01-0.03) vs 0.09 (0.06-0.12) × 10^9/L, p < 0.01) at admission. Critically injured patients who developed MODS (n = 27) had higher interferon gamma (IFN-γ) concentrations at admission, compared with patients of matched injury severity and shock (n = 60) who did not develop MODS (MODS vs no MODS: 4.1 (1.8-9.0) vs 1.0 (0.6-1.8) pg/ml, p = 0.01). Lymphopenia was observed within 24 h of injury and was persistent in those who developed MODS. Patients with a lymphocyte count of 0.5 × 10(9)/L or less at 48 h, had a 45 % mortality rate.
CONCLUSIONS
This study provides evidence of lymphocyte activation within 2 h of injury, as demonstrated by increased NK dim cells, reduced γδ-low T lymphocytes and high blood IFN-γ concentration. These changes are associated with the development of MODS and lymphopenia. The study reveals new opportunities for investigation to characterise the cellular response to trauma and examine its influence on recovery.
背景
随着复苏策略的完善,严重创伤后的早期存活率有所提高。多器官功能障碍综合征(MODS)在这群脆弱的患者中很常见,会导致住院时间延长和晚期死亡。创伤后MODS广泛归因于炎症调节失调,但这种反应的确切机制及其对器官损伤的影响尚不完全清楚。本研究旨在调查入院期间早期淋巴细胞反应与MODS发生之间的关系。
方法
在24个月期间,从城市主要创伤中心招募创伤患者,纳入一项正在进行的观察性队列研究。在受伤后2小时内且在包括输血在内的院内干预之前采集入院血样。研究人群以男性为主,损伤机制为钝性伤。使用流式细胞术鉴定淋巴细胞亚群,包括辅助性T细胞、细胞毒性T细胞、自然杀伤细胞和γδT细胞。还检查了入院后前7天的早期细胞因子释放和淋巴细胞计数。
结果
本研究表明,发生MODS的创伤患者入院时NKdim细胞数量增加(MODS组与未发生MODS组:22%对13%,p<0.01),γδ低T细胞减少(MODS组与未发生MODS组:0.02(0.01 - 0.03)对0.09(0.06 - 0.12)×10^9/L,p<0.01)。与损伤严重程度和休克程度匹配但未发生MODS的患者(n = 60)相比,发生MODS的重伤患者(n = 27)入院时干扰素γ(IFN - γ)浓度更高(MODS组与未发生MODS组:4.1(1.8 - 9.0)对1.0(0.6 - 1.8)pg/ml,p = 0.01)。伤后24小时内观察到淋巴细胞减少,且在发生MODS的患者中持续存在。伤后48小时淋巴细胞计数为0.5×10(9)/L或更低的患者死亡率为45%。
结论
本研究提供了伤后2小时内淋巴细胞激活的证据,表现为NKdim细胞增加、γδ低T淋巴细胞减少和血液IFN - γ浓度升高。这些变化与MODS的发生和淋巴细胞减少有关。该研究揭示了新的研究机会,以表征细胞对创伤的反应并检查其对恢复的影响。
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