Cardiopulmonary bypass decreases cytokine production in lipopolysaccharide-stimulated whole blood cells:: Roles of interleukin-10 and the extracorporeal circuit

Cardiopulmonary bypass decreases cytokine production in lipopolysaccharide-stimulated whole blood cells:: Roles of interleukin-10 and the extracorporeal circuit
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DOI:
10.1097/00003246-200006000-00004
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发表时间:
2000-06-01
影响因子:
8.8
通讯作者:
Philip, I
Philip, I
中科院分区:
医学1区
文献类型:
--
作者:
Dehoux, MS;Hernot, S;Philip, I

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目的:确定心肺旁路 (CPB) 是否会改变脂多糖 (LPS) 刺激的全血细胞离体细胞因子的产生,并评估白细胞介素 (IL)-10 和体外循环 (EGG) 在这种改变中的作用。设计:前瞻性对照研究。环境:一所大学医院的生物化学实验室和外科重症监护病房。患者:连续 17 名接受常温 CPB 和瓣膜手术的成人患者八名健康志愿者。 干预措施:在 CPB 之前和期间(60、90、120、180 和 360 分钟)从患者身上抽取用于细胞因子测量的血样,并在有和没有 LPS 以及有和没有抗 IL-10 抗体的情况下进行培养。还从健康受试者中抽取血液,并在分离的 EGG 中循环之前和期间进行远细胞因子分析。 测量和主要结果:通过酶联免疫吸附测定法测量的离体肿瘤坏死因子 (TNF)-α、IL-6、IL-8 和 IL-10 的浓度在两个实验设置中均降低。在接受 GPB 的患者中,LPS 高反应性在 GPB 开始后 60 分钟时检测到,并在 120 分钟时达到最大(与 CPB 前水平相比下降 78% 至 86%),但这种反应是短暂的,TNF-α 除外。 IL-10 的血浆浓度在 CPB 开始后 90 分钟达到峰值,但 IL-10 在 LPS 反应低下中的作用似乎有限,因为抗 IL-10 抗体显着增加离体 IL-6 的产生,但不增加 TNF-α 或 IL-8 的产生。在孤立的 ECC 研究中,血浆中未检测到 IL-10,但细胞因子(IL-8 除外)的离体产生量减少(66% 至 95%)。结论:我们的结果表明:a) 根据细胞因子产生量的测量,GPB 诱导全血早期且短暂的 LPS 低反应性; b) IL-10似乎只部分参与了这一过程,其作用仅限于活体情况; c) 血液与 ECC 的接触足以诱发 LPS 低反应性。
Objective: To determine whether cardiopulmonary bypass (CPB) alters the ex vivo cytokine production of whole blood cells stimulated by lipopolysaccharide (LPS) and to assess the roles of interleukin (IL)-10 and an extracorporeal circuit (EGG) in the alteration.Design: Prospective, controlled study.Setting: Biochemistry laboratory and surgical intensive care unit in a university hospital.Patients: Seventeen consecutive adult patients undergoing coronary artery bypass grafting or valve surgery with normothermic CPB and eight healthy volunteers.interventions: Blood samples for cytokine measurement were drawn from patients before and during (at 60, 90, 120, 180 and 360 mins) CPB and were cultured with and without LPS and with and without anti-IL-10 antibodies. Blood was also drawn from healthy subjects and sampled far cytokine analysis before and during circulation in an isolated EGG.Measurements and Main Results: The concentrations of ex vivo tumor necrosis factor (TNF)-alpha, IL-6, IL-8, and IL-10, measured by enzyme-linked immunosorbent assay, were reduced in both experimental settings. In patients on GPB, LPS hyperesponsiveness was detected at 60 mins after the onset of GPB and was maximal at 120 mins (78% to 86% decreases from pre-CPB levels) but was transient, except for TNF-alpha. The plasma concentration of IL-10 peaked at 90 mins after the start of CPB, but the role of IL-10 in LPS hyporesponsiveness appears limited because anti-IL-10 antibodies significantly increased ex vivo production of IL-6 but not TNF-alpha or IL-8. In the isolated ECC study, no IL-10 was detected in plasma, yet the ex vivo production of the cytokines (except IL-8) was decreased (by 66% to 95%).Conclusion: Our results demonstrate the following: a) GPB induces an early and transient LPS hyporesponsiveness of whole blood as measured by cytokine production; b) IL-10 seems only partly involved in this process, and its role is restricted to an in vive situation; and c) contact of blood with an ECC is sufficient to induce LPS hyporesponsiveness.