Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610-0019, USA.
Methods. 2013 May 15;61(1):3-9. doi: 10.1016/j.ymeth.2013.04.024. Epub 2013 May 11.
For the past thirty years, since IL-1β and TNFα were first cloned, there have been efforts to measure plasma cytokine concentrations in patients with severe sepsis and trauma, and to use these measurements to predict clinical outcome and response to therapies. The numbers of cytokines and chemokines that have been measured in the plasma have literally exploded with the development of multiplex immune approaches. Dozens of relatively small cohort studies have shown plasma cytokine concentrations correlating with outcome in sepsis and trauma. Despite what appears to be a consensus that plasma cytokine concentrations should be useful in the clinical setting, only two cytokines, IL-6 and procalcitonin, have approached routine clinical use. IL-6 has been used as a research tool for entry into sepsis-intervention trials, while procalcitonin is being used clinically at a large number of institutions to distinguish sepsis from other inflammatory processes. For most cytokines, the relative lack of sensitivity and specificity of individual or multiplex cytokine measurements has hindered their utility to predict clinical trajectory in individual patients. The problem rests with a general misunderstanding of cytokine biology, failing to appreciate the general paracrine nature of these mediators, the presence of binding proteins, chaperones and inhibitors in the plasma, and the rapid clearance of these proteins by binding to cell receptors and clearance predominantly by the kidney. The future of using plasma cytokine measurements as an indicator of sepsis/trauma severity or predicting outcome is generally behind us, although there is optimism that procalcitonin measurements may ultimately prove to have utility in the diagnosis of severe sepsis.
在过去的三十年中，自从首次克隆出白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNFα）以来，人们一直致力于测量严重脓毒症和创伤患者的血浆细胞因子浓度，并利用这些测量值来预测临床结果和对治疗的反应。随着多重免疫方法的发展，已经测量了大量的细胞因子和趋化因子。数十项相对较小的队列研究表明，血浆细胞因子浓度与脓毒症和创伤的结局相关。尽管似乎存在共识，即血浆细胞因子浓度在临床环境中应该是有用的，但只有两种细胞因子，白细胞介素-6（IL-6）和降钙素原，已经接近常规临床使用。IL-6 已被用作进入脓毒症干预试验的研究工具，而降钙素原则在许多机构中被用于临床，以区分脓毒症与其他炎症过程。对于大多数细胞因子而言，单个或多重细胞因子测量的相对缺乏敏感性和特异性，阻碍了其在预测个体患者临床轨迹中的实用性。问题在于对细胞因子生物学的普遍误解，未能理解这些介质的一般旁分泌性质，血浆中存在结合蛋白、伴侣蛋白和抑制剂，以及这些蛋白质通过与细胞受体结合和主要通过肾脏清除而迅速清除。使用血浆细胞因子测量值作为脓毒症/创伤严重程度的指标或预测结果的未来普遍落后，尽管有人乐观地认为降钙素原测量最终可能证明在严重脓毒症的诊断中有实用性。
