Belikova Ioulia, Lukaszewicz Anne Claire, Faivre Valerie, Damoisel Charles, Singer Mervyn, Payen Didier
Department of Anesthesiology and Critical Care, Lariboisière University Hospital, Paris, France.
Crit Care Med. 2007 Dec;35(12):2702-8. doi: 10.1097/01.ccm.0000295593.25106.c4.
During sepsis, after an initial stimulation immune cells down-regulate their functions, leading to a state of immunosuppression. Because the mechanisms of such down-regulation are unclear, we investigated the hypothesis of an energetic failure of immune cells to participate in immune dysfunction.
Cohort of septic shock patients to study peripheral blood mononuclear cells (PBMCs) biological energy in comparison to healthy volunteer cells.
Critical care unit and laboratory, university hospital.
Eighteen severe sepsis or septic shock patients and 32 healthy volunteers.
Ex vivo measurement of oxygen consumption in PBMCs taken from patients. The PBMCs' mitochondrial oxidative phosphorylation was investigated using adenosine diphosphate stimulation. The plasma factors implication was tested, using healthy cells incubated in septic plasma, or septic cells incubated in healthy plasma, at different time points of sepsis. The relationship between monocyte human leukocyte antigen-DR expression and bioenergetic results was tested.
Baseline oxygen consumption was higher in septic PBMCs (p < .01), with an attenuated response to adenosine diphosphate stimulation (p < .01). Oxygen consumption of healthy PBMCs incubated in septic plasma mimicked the septic cell response, with amplitude depending on the duration of sepsis (days 0-28). Septic cells incubated in healthy plasma partially recovered normal patterns. Septic plasma incubation increased the fraction of decoupling oxygen consumption (p = .021). A relationship between oxygen consumption (baseline or adenosine diphosphate stimulated) and human leukocyte antigen-DR expression was observed for incubation with plasma sampled at different time points of septic shock.
Energetic failure of PBMCs in sepsis may be a factor associated with the modulation of immune response and human leukocyte antigen-DR phenotype, partially driven by plasma factors.
在脓毒症期间，免疫细胞在初始刺激后会下调其功能，导致免疫抑制状态。由于这种下调机制尚不清楚，我们研究了免疫细胞能量衰竭参与免疫功能障碍的假说。
脓毒性休克患者队列，用于研究外周血单核细胞（PBMC）与健康志愿者细胞相比的生物能量。
大学医院重症监护病房和实验室。
18例严重脓毒症或脓毒性休克患者和32名健康志愿者。
对取自患者的PBMC进行体外耗氧量测量。使用二磷酸腺苷刺激研究PBMC的线粒体氧化磷酸化。在脓毒症的不同时间点，使用在脓毒症血浆中孵育的健康细胞或在健康血浆中孵育的脓毒症细胞，测试血浆因子的影响。测试单核细胞人类白细胞抗原-DR表达与生物能量结果之间的关系。
脓毒症PBMC的基线耗氧量较高（p <.01），对二磷酸腺苷刺激的反应减弱（p <.01）。在脓毒症血浆中孵育的健康PBMC的耗氧量模拟了脓毒症细胞的反应，其幅度取决于脓毒症的持续时间（第零至28天）。在健康血浆中孵育的脓毒症细胞部分恢复了正常模式。脓毒症血浆孵育增加了解偶联耗氧量的比例（p = 0.021）。在脓毒性休克的不同时间点采集血浆进行孵育时，观察到耗氧量（基线或二磷酸腺苷刺激）与人类白细胞抗原-DR表达之间的关系。
脓毒症中PBMC的能量衰竭可能是与免疫反应调节和人类白细胞抗原-DR表型相关的一个因素，部分由血浆因子驱动。
