Seghaye M, Duchateau J, Bruniaux J, Demontoux S, Bosson C, Serraf A, Lecronier G, Mokhfi E, Planche C
Department of Pediatric Cardiac Intensive Care, Centre Chirurgical Marie-Lannelongue, Le Plessis-Robinson, France.
J Thorac Cardiovasc Surg. 1996 Mar;111(3):545-53. doi: 10.1016/s0022-5223(96)70306-9.
To evaluate cytokine balance related to cardiopulmonary bypass, we prospectively investigated 11 infants undergoing cardiac operations for congenital heart disease. Proinflammatory cytokines (tumor necrosis factor-alpha and interleukin-8) and the antiinflammatory cytokine interleukin-10 were measured at multiple time points before, during, and after bypass. Tumor necrosis factor-alpha and interleukin-8 values were within normal range before the operation. These values increased significantly during bypass, reaching their peaks after protamine administration (tumor necrosis factor-alpha, 133.6 +/- 124.9 pg/ml; mean +/- standard deviation; p<0.005) and 2 hours after termination of the procedure (interleukin-8, 92.1 +/- 44.1 pg/ml; p < 0.01). Tumor necrosis factor-alpha and interleukin-8 equaled normal prebypass values from the first postoperative day on. Interleukin-10 levels were within normal range before the operation and were already significantly increased 10 minutes after initiation of bypass (interleukin 10, 39.4 +/- 34.3 pg/ml; p<0.05). These levels remained elevated throughout the procedure but returned to normal after protamine administration. A second significant release of interleukin-10 occurred from the early postoperative period on, reaching its peak 24 hours after termination of cardiopulmonary bypass (interleukin-10, 351.6 +/- 304.0 pg/ml; p < 0.01). Interleukin-10 values were normal on the second postoperative day in all patients. Interleukin-10 kinetics showed an inverse pattern compared with tumor necrosis factor-alpha and interleukin-8. This difference suggests an interplay between proinflammatory and antiinflammatory cytokines released during and after cardiopulmonary bypass. Interleukin-10 levels measured 4 and 24 hours after bypass strongly correlated with the degree of hypothermia during bypass (Spearman's correlation coefficient, -0.77 [p < 0.01] and -0.89 [p < 0.0005], respectively); these levels did not correlate with duration of bypass and aortic crossclamping, however. This result suggests that besides immunologically mediated production of interleukin-10, hypothermia itself could modulate interleukin-10 production. In conclusion, this study demonstrates interleukin-10 production, in addition to interleukin-8 and tumor necrosis factor-alpha synthesis, in response to cardiopulmonary bypass in infants. Interleukin-10 could play a protective role by down-regulating proinflammatory cytokine release during and after cardiopulmonary bypass.
为评估与体外循环相关的细胞因子平衡，我们前瞻性地研究了11例接受先天性心脏病心脏手术的婴儿。在体外循环前、期间和之后的多个时间点测量促炎细胞因子（肿瘤坏死因子-α和白细胞介素-8）以及抗炎细胞因子白细胞介素-10。肿瘤坏死因子-α和白细胞介素-8值在手术前处于正常范围内。这些值在体外循环期间显著升高，在给予鱼精蛋白后达到峰值（肿瘤坏死因子-α，133.6±124.9 pg/ml；平均值±标准差；p<0.005）以及在手术结束后2小时（白细胞介素-8，92.1±44.1 pg/ml；p<0.01）。从术后第一天起，肿瘤坏死因子-α和白细胞介素-8等于体外循环前的正常水平。白细胞介素-10水平在手术前处于正常范围内，并且在体外循环开始后10分钟就已显著升高（白细胞介素10，39.4±34.3 pg/ml；p<0.05）。这些水平在整个手术过程中持续升高，但在给予鱼精蛋白后恢复正常。白细胞介素-10的第二次显著释放从术后早期开始，在体外循环结束后24小时达到峰值（白细胞介素-10，351.6±304.0 pg/ml；p<0.01）。所有患者术后第二天白细胞介素-10值均正常。白细胞介素-10的动力学表现出与肿瘤坏死因子-α和白细胞介素-8相反的模式。这种差异表明在体外循环期间和之后释放的促炎和抗炎细胞因子之间存在相互作用。在体外循环后4小时和24小时测量的白细胞介素-10水平与体外循环期间的低温程度密切相关（Spearman相关系数分别为-0.77 [p<0.01] 和-0.89 [p<0.0005]）；然而，这些水平与体外循环持续时间和主动脉阻断时间无关。这一结果表明，除了免疫介导的白细胞介素-10产生外，低温本身可能调节白细胞介素-10的产生。总之，本研究证明了婴儿在体外循环时除了白细胞介素-8和肿瘤坏死因子-α合成外，还产生白细胞介素-10。白细胞介素-10可能通过在体外循环期间和之后下调促炎细胞因子的释放发挥保护作用。
