1Department of Intensive Care, University Hospital Rigshospitalet, Copenhagen Ø, Denmark. 2Centre of Inflammation and Metabolism, Department of Infectious Diseases M7641, University Hospital Rigshospitalet, Copenhagen Ø, Denmark. 3Neurovascular Research Laboratory, Faculty of Health, Science and Sport, University of Glamorgan, South Wales, United Kingdom. 4Centre for Clinical Education, University of Copenhagen and the Capital Region of Denmark, Copenhagen, Denmark. 5The Heart Centre, Department of Lung Transplantation, University Hospital Rigshospitalet, Copenhagen Ø, Denmark. 6Laboratory of Molecular Medicine, Department of Clinical Immunology M7631, University Hospital Rigshospitalet, Copenhagen Ø, Denmark. 7Neurointensive Care Unit 2093, Department of Neuroanesthesiology, University Hospital Rigshospitalet, Copenhagen Ø, Denmark.
Crit Care Med. 2014 Jul;42(7):1658-65. doi: 10.1097/CCM.0000000000000320.
Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following lipopolysaccharide-induced pulmonary and systemic inflammation.
Randomized, double-blind, placebo-controlled, crossover study.
Healthy male volunteers.
Fifteen volunteers (mean age, 23; SD, 2 yr) received Escherichia coli endotoxin (lipopolysaccharide, 4 ng/kg) IV or endobronchially on two different study days. Groups were evaluated by bronchoalveolar lavage at baseline (0 hr) and 2, 4, 6, 8, or 24 hours postchallenge. Cardiorespiratory variables were continuously recorded throughout the study day, and plasma and bronchoalveolar lavage fluid markers of inflammation were measured.
IV endotoxin elicited a systemic inflammatory response with a time-dependent increase and peak in tumor necrosis factor-α, interleukin-6, and leukocyte counts (all p < 0.001). Furthermore, a delayed (6-8 hr) increase in bronchoalveolar lavage fluid interleukin-6 concentration (p < 0.001) and alveolar leukocyte count (p = 0.03) and a minor increase in bronchoalveolar lavage fluid tumor necrosis factor-α were observed (p = 0.06). Endobronchial endotoxin was followed by progressive alveolar neutrocytosis and increased bronchoalveolar lavage fluid tumor necrosis factor-α, interleukin-6, and albumin (all p < 0.001); a systemic inflammatory response was observed after 2-4 hours, with no change in plasma tumor necrosis factor-α.
Acute lung or systemic inflammation in humans is followed by a transcompartmental proinflammatory response, the degree and differential kinetics of which suggests that the propagation of inflammation may depend on the primary site of injury.
早期炎症期间的跨室信号可能导致疾病向其他器官传播。其时间过程和涉及的机制仍知之甚少。我们旨在比较人类脂多糖诱导的肺和全身炎症后急性跨室炎症反应。
随机、双盲、安慰剂对照、交叉研究。
重症监护病房（ICU）中的受试者：健康男性志愿者。
15 名志愿者（平均年龄 23 岁；标准差 2 岁）在两天的不同研究日接受大肠杆菌内毒素（脂多糖，4ng/kg）静脉内或支气管内给药。在基线（0 小时）和挑战后 2、4、6、8 或 24 小时通过支气管肺泡灌洗对两组进行评估。整个研究日连续记录心肺变量，并测量血浆和支气管肺泡灌洗液中的炎症标志物。
静脉内内毒素引起全身炎症反应，肿瘤坏死因子-α、白细胞介素-6 和白细胞计数呈时间依赖性增加和达到峰值（均 p<0.001）。此外，支气管肺泡灌洗液白细胞介素-6 浓度（p<0.001）和肺泡白细胞计数（p=0.03）延迟（6-8 小时）增加，支气管肺泡灌洗液肿瘤坏死因子-α略有增加（p=0.06）。支气管内内毒素后，出现进行性肺泡中性粒细胞增多和支气管肺泡灌洗液肿瘤坏死因子-α、白细胞介素-6 和白蛋白增加（均 p<0.001）；2-4 小时后观察到全身炎症反应，血浆肿瘤坏死因子-α无变化。
人类急性肺或全身炎症后会发生跨室促炎反应，其程度和差异动力学表明炎症的传播可能取决于损伤的主要部位。
