Holzheimer R G, Gross J, Schein M
Department of General Surgery, University of Halle, Germany.
Shock. 1999 May;11(5):305-10. doi: 10.1097/00024382-199905000-00001.
In traumatized and septic patients, excessive cytokine production may lead to organ dysfunction and death. Current understanding of cytokine kinetics with regard to clinical scenarios, however, is still limited by a paucity of studies investigating the cytokine levels in humans with inflammation-reperfusion injury in the absence of infection. Our hypothesis was that endotoxin is introduced into circulation during and after abdominal aortic aneurysm (AAA) repair and is associated with pro- and anti-inflammatory cytokine-response. The purpose of this prospective pilot study in 10 patients who underwent elective AAA repair was to assess organ function and immune response to systemic endotoxemia after the operation by measuring endotoxin, endotoxin neutralizing capacity (ENC), tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-10, and TNF-RI and II. Blood samples were obtained from indwelling catheters or direct venipuncture preoperatively, perioperatively (8 time points) until the second postoperative day. Endotoxin and ENC were determined by a special kinetic Limulus amoebocyte lysate (LAL) assay and TNF-alpha, IL-6, IL-10, and TNF-RI and II by commercial ELISA. Endotoxin levels were significantly elevated after declamping and 90 min after clamping of the aorta (2.3 + .9 pg/mL; 5.4+/-3.6 pg/mL). ENC decreased to the lowest levels at 90 min after clamping. TNF-alpha levels were maximal, but not significantly elevated, 120 min after clamping. IL-6 increased significantly during the operation and reached maximum levels (189.8+/-47 pg/mL) at the first postoperative day. Anti-inflammatory IL-10 and TNF-RI and II were elevated early during the operation. The changes in cytokine levels were associated with mild organ dysfunction. We conclude that AAA repair is associated with endotoxin, proinflammatory, and an almost coincidental anti-inflammatory cytokine release, providing baseline data about what constitutes an appropriate immune response. Such responses to trauma and ischemia-reperfusion need to be further investigated before attempting immunomodulation.
在创伤和脓毒症患者中，细胞因子过度产生可能导致器官功能障碍和死亡。然而，目前对于临床情况下细胞因子动力学的认识，仍受限于缺乏对无感染的炎症再灌注损伤患者体内细胞因子水平的研究。我们的假设是，在腹主动脉瘤（AAA）修复过程中和修复后，内毒素进入循环系统，并与促炎和抗炎细胞因子反应相关。这项针对10例行择期AAA修复患者的前瞻性初步研究的目的，是通过测量内毒素、内毒素中和能力（ENC）、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-10以及TNF-RI和TNF-RII，评估术后器官功能和对全身内毒素血症的免疫反应。术前、围手术期（8个时间点）直至术后第二天，从留置导管或直接静脉穿刺获取血样。内毒素和ENC通过特殊的动态鲎试剂法测定，TNF-α、IL-6、IL-10以及TNF-RI和TNF-RII通过商业酶联免疫吸附测定法测定。主动脉夹闭解除后以及夹闭90分钟后，内毒素水平显著升高（分别为2.3±0.9 pg/mL；5.4±3.6 pg/mL）。夹闭90分钟时，ENC降至最低水平。夹闭120分钟时，TNF-α水平达到峰值，但无显著升高。IL-6在手术期间显著增加，并在术后第一天达到最高水平（189.8±47 pg/mL）。抗炎性IL-10以及TNF-RI和TNF-RII在手术早期升高。细胞因子水平的变化与轻度器官功能障碍相关。我们得出结论，AAA修复与内毒素、促炎细胞因子以及几乎同时出现的抗炎细胞因子释放有关，为构成适当免疫反应的因素提供了基线数据。在尝试进行免疫调节之前，需要进一步研究对创伤和缺血再灌注的此类反应。
