Tang G J
Department of Anesthesiology, Veterans General Hospital-Taipei, Taiwan, R.O.C.
Acta Anaesthesiol Sin. 1996 Sep;34(3):141-9.
Both trauma and infection cause a rise in body temperature, white blood cell count, acute phase proteins, fluid and sodium retention and negative nitrogen balance. This phenomenon is often described as "acute phase response" or "systemic inflammatory response syndrome" to denote a coordinated systemic response to significant tissue injury and/or microbial invasion. It is generally agreed that the acute phase response is mediated through the interaction of cytokine and neuroendocrine pathways. Tumor Necrosis Factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are two of the major key cytokines involved in the generation of acute phase response. Interleukin-6 are consistently found in septic, trauma and post-operative patients and correlated well with the severity of sepsis or injury. IL-6 is responsible for the fever and metabolic changes in the acute phase. In addition to IL-6, TNF-alpha was proved to be the mediator that orchestrates the hemodynamic and tissue injury in septic shock. TNF-alpha destroys endothelial cells and induces disseminated intravascular coagulation, fluid shift, shock, multiple organ system failure and death. On many clinical occasions, both infection and trauma may happen simultaneously on the same patient. Our study demonstrated that operation on the infected patients would cause a synergistic effect on both TNF-alpha and IL-6 levels. The pulse increase in TNF-alpha and the persistent elevation of IL-6 were responsible for the post-operative unstable clinical condition in the infected patients. Should we block the cytokine signal and inflammatory response that appear to be harmful? Animal studies have shown that the septic shock to endotoxin challenge can be prevented by pretreatment with monoclonal antibody against TNF-alpha. The transcription of TNF-alpha can be blocked with corticosteroid in vivo. The post-operative increase in IL-6 and its related inflammation can be attenuated with corticosteroid, epidural anesthesia and narcotics. However, although blocking the inflammatory response has a beneficial effect of stress free it also eliminates our ability to fight with bacterial infection by lowering our immune response. How to manipulate these cytokines is a question of art more than science.
创伤和感染都会导致体温升高、白细胞计数增加、急性期蛋白升高、液体和钠潴留以及负氮平衡。这种现象通常被描述为“急性期反应”或“全身炎症反应综合征”，以表示对严重组织损伤和/或微生物入侵的协调性全身反应。人们普遍认为，急性期反应是通过细胞因子和神经内分泌途径的相互作用介导的。肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）是参与急性期反应产生的两个主要关键细胞因子。在脓毒症、创伤和术后患者中始终能检测到白细胞介素-6，且其与脓毒症或损伤的严重程度密切相关。IL-6 是急性期发热和代谢变化的原因。除了 IL-6 之外，TNF-α 被证明是在脓毒性休克中协调血流动力学和组织损伤的介质。TNF-α 会破坏内皮细胞并引发弥散性血管内凝血、液体转移、休克、多器官系统衰竭和死亡。在许多临床情况下，感染和创伤可能会在同一患者身上同时发生。我们的研究表明，对感染患者进行手术会对 TNF-α 和 IL-6 水平产生协同作用。TNF-α 的脉冲式升高和 IL-6 的持续升高是感染患者术后临床状况不稳定的原因。我们是否应该阻断似乎有害的细胞因子信号和炎症反应呢？动物研究表明，用抗 TNF-α 单克隆抗体进行预处理可以预防内毒素攻击所致的脓毒性休克。体内使用皮质类固醇可以阻断 TNF-α 的转录。使用皮质类固醇、硬膜外麻醉和麻醉剂可以减轻术后 IL-6 的升高及其相关炎症。然而，尽管阻断炎症反应具有无应激的有益效果，但它也会通过降低我们的免疫反应而削弱我们对抗细菌感染的能力。如何操控这些细胞因子更多的是一门艺术而非科学问题。
