Grundmann U, Rensing H, Adams H A, Falk S, Wendler O, Ebinger N, Bauer M
Department of Anesthesiology and Critical Care Medicine, University of Saarland, Homburg, Germany.
Anesthesiology. 2000 Aug;93(2):359-69. doi: 10.1097/00000542-200008000-00013.
The ability of leukocytes to release proinflammatory cytokines on lipopolysaccharide stimulation in vitro is impaired after cardiopulmonary bypass (CPB). This study tested contribution and interaction of humoral factors in altered leukocyte responsiveness to lipopolysaccharide.
Whole blood and isolated peripheral-blood mononuclear cells (PBMCs) from 10 patients obtained after induction of anesthesia (T1) and 20 min (T2) and 24 h (T3) after CPB were cultured in the absence or presence of lipopolysaccharide and assessed for release of tumor necrosis factor alpha (TNF-alpha) and interleukin (IL)-1beta and their functional antagonists, IL-1 receptor antagonist (IL-1ra) and IL-10. In addition, dose-response characteristics and interaction of IL-10 and norepinephrine as modulators of TNF-alpha release were studied.
Cardiopulmonary bypass induced release of antiinflammatory (T2: IL-10: median 25 pg/ml, 25th-75th percentile 9-42; IL-1ra: median 1,528 pg/ml, 25th-75th percentile 1,075-17,047; P < 0.05 compared with T1) but failed to induce proinflammatory cytokines (T2: TNF-alpha: median 0 pg/ml, 25th-75th percentile 0-6; IL-1beta: median 1 pg/ml, 25th-75th percentile 0-81; nonsignificant). Removal of plasma at T2 increased TNF-alpha response to lipopolysaccharide (+83.8%; P < 0.05), whereas it suppressed IL-10 (-36.8%; P < 0.05). Similarly, incubation of PBMCs (T1) with plasma obtained after CPB (T2) as well as addition of IL-10 or norepinephrine in concentrations present in plasma after CPB led to a reduced lipopolysaccharide-stimulated TNF-alpha and an increased IL-10 response. Coadministration of norepinephrine and IL-10 had synergistic effects. Although pretreatment with an anti-IL-10 antibody and labetalol before addition of plasma obtained at T2 largely restored the TNF-alpha response in vitro, their addition post-treatment failed to restore the monocytic TNF-alpha response.
Plasma contains interacting factors that inhibit the release of TNF-alpha and increase the release of IL-10, presumably attenuating the inflammatory response to CPB. Although norepinephrine fails to induce a cytokine response in the absence of other stimuli, its administration seems to augment the antiinflammatory IL-10 response while attenuating the TNF-alpha response.
体外循环（CPB）后，白细胞在脂多糖刺激下释放促炎细胞因子的能力受损。本研究测试了体液因子在白细胞对脂多糖反应性改变中的作用及相互作用。
采集10例患者在麻醉诱导后（T1）、CPB后20分钟（T2）和24小时（T3）的全血及分离的外周血单核细胞（PBMC），在有无脂多糖的情况下进行培养，评估肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-1β及其功能拮抗剂IL-1受体拮抗剂（IL-1ra）和IL-10的释放。此外，研究了IL-10和去甲肾上腺素作为TNF-α释放调节剂的剂量反应特征及相互作用。
体外循环诱导了抗炎因子的释放（T2：IL-10：中位数25 pg/ml，第25-75百分位数9-42；IL-1ra：中位数1528 pg/ml，第25-75百分位数1075-17047；与T1相比，P<0.05），但未诱导促炎细胞因子释放（T2：TNF-α：中位数0 pg/ml，第25-75百分位数0-6；IL-1β：中位数1 pg/ml，第25-75百分位数0-81；无统计学意义）。T2时去除血浆可增加TNF-α对脂多糖的反应（+83.8%；P<0.05），而抑制IL-10（-36.8%；P<0.05）。同样，将CPB后（T2）获得的血浆与PBMC（T1）一起孵育，以及添加CPB后血浆中存在浓度的IL-10或去甲肾上腺素，会导致脂多糖刺激的TNF-α降低，IL-10反应增加。去甲肾上腺素和IL-10联合给药具有协同作用。虽然在添加T2获得的血浆前用抗IL-10抗体和拉贝洛尔预处理在很大程度上恢复了体外TNF-α反应，但在处理后添加它们未能恢复单核细胞TNF-α反应。
血浆中含有相互作用的因子，可抑制TNF-α释放并增加IL-10释放，可能减弱对CPB的炎症反应。虽然去甲肾上腺素在没有其他刺激时不能诱导细胞因子反应，但其给药似乎增强了抗炎性IL-10反应，同时减弱了TNF-α反应。
