Systemic release of cytokines and heat shock proteins in porcine models of polytrauma and hemorrhage
Systemic release of cytokines and heat shock proteins in porcine models of polytrauma and hemorrhage
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DOI：
10.1097/ccm.0b013e318232e314
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发表时间：
2012-03-01
影响因子：
8.8
通讯作者：
Majetschak, Matthias
中科院分区：
文献类型：
--
作者：
Baker, Todd A.;Romero, Jacqueline;Majetschak, Matthias
目的：确定一组细胞因子和热休克蛋白在猪多创伤/出血模型中的全身释放动力学，并评估它们是否可以作为早期创伤生物标志物。设计：前瞻性观察研究。环境：研究实验室。实验对象：21头约克郡猪。干预措施:没有。测量和主要结果：猪经历了多发伤（股骨骨折/肺挫伤，P）、出血（平均动脉压25-30 mm Hg， H）、多发伤合并出血（P/H）或假手术(S)。在无干预的60分钟休克期间，在基线时每隔5- 15分钟采集一次血浆；在长达300分钟的液体复苏期间，每隔60- 120分钟采集一次血浆。采用酶联免疫吸附法检测血浆中白细胞介素-10、白细胞介素-4、白细胞介素-5、白细胞介素-6、白细胞介素-8、白细胞介素-10、白细胞介素-12/白细胞介素-23p40、白细胞介素-13、白细胞介素-17、白细胞介素-18、干扰素γ、转化生长因子- β、肿瘤坏死因子- α、热休克蛋白40、热休克蛋白70和热休克蛋白90的含量。S、P、H后均成活（n = 5/组）。P/H后的6只动物中有3只死亡。在P后休克期间，白细胞介素-10升高，H后这种升高减弱。在P、H和s后休克期间，肿瘤坏死因子- α升高，P/H消除全身白细胞介素-10和肿瘤坏死因子- α的释放，导致休克期间白细胞介素-6水平升高20%至30%。随着液体复苏的开始，P、H和P/H后肿瘤坏死因子- α和白细胞介素-10水平下降；P处理后热休克蛋白70升高；结论：多发伤和/或出血后全身细胞因子释放的差异调节，结合复苏的影响，可以解释创伤患者全身细胞因子/热休克蛋白水平与临床变量的变异性和不一致的相关性。严重程度（P/H）的损伤部分抑制全身炎症反应。在猪创伤模型中，测量到的细胞因子/热休克蛋白的血浆浓度不能反映损伤的严重程度或生理变化，也不太可能作为有用的创伤生物标志物。（危重医学2012；40:876-885）
Objective: To define systemic release kinetics of a panel of cytokines and heat shock proteins in porcine polytrauma/hemorrhage models and to evaluate whether they could be useful as early trauma biomarkers.Design: Prospective observational study.Setting: Research laboratory.Subjects: Twenty-one Yorkshire pigs.Interventions: None.Measurements and Main Results: Pigs underwent polytrauma (femur fractures/lung contusion, P), hemorrhage (mean arterial pressure 25-30 mm Hg, H), polytrauma plus hemorrhage (P/H), or sham procedure (S). Plasma was obtained at baseline, in 5- to 15-min intervals during a 60-min shock period without intervention, and in 60- to 120-min intervals during fluid resuscitation for up to 300 min. Plasma was assayed for interleukin-10, interleukin-4, interleukin-5, interleukin-6, interleukin-8, interleukin-10, interleukin-12/interleukin-23p40, interleukin-13, interleukin-17, interleukin-18, interferon gamma, transforming growth factor-beta, tumor necrosis factor-alpha, heat shock protein 40, heat shock protein 70, and heat shock protein 90 by enzyme-linked immunosorbent assay. All animals after S, P, and H survived (n = 5/group). Three of six animals after P/H died. Interleukin-10 increased during shock after P and this increase was attenuated after H. Tumor necrosis factor-alpha increased during the shock period after P, H, and also after S. P/H abolished the systemic interleukin-10 and tumor necrosis factor-alpha release and resulted in 20% to 30% increased levels of interleukin-6 during shock. As fluid resuscitation was initiated, tumor necrosis factor-alpha and interleukin-10 levels decreased after P, H, and P/H; heat shock protein 70 increased after P; and interleukin-6 levels remained elevated after P/H and also increased after P and S.Conclusions: Differential regulation of the systemic cytokine release after polytrauma and/or hemorrhage, in combination with the effects of resuscitation, can explain the variability and inconsistent association of systemic cytokine/heat shock protein levels with clinical variables in trauma patients. Insults of major severity (P/H) partially suppress the systemic inflammatory response. The plasma concentrations of the measured cytokines/heat shock proteins do not reflect injury severity or physiological changes in porcine trauma models and are unlikely to be able to serve as useful trauma biomarkers in patients. (Crit Care Med 2012; 40: 876-885)