Intensivist University Hospital, Vrije Universiteit Brussel (VUB), Brussels, Belgium.
Mol Med. 2012 Dec 20;18(1):1363-5. doi: 10.2119/molmed.2012.00300.
For almost three decades, researchers have invested in strategies that involved removal of excess inflammatory mediators from the circulation (that is, the "cytotoxic" approach). Blood purification techniques using an extracorporeal device can indeed non-specifically remove a wide array of inflammatory mediators from the circulation. In animal models, this multimediator targeting or pleiotropic approach was shown to downregulate systemic inflammation and to restore immune homeostasis. In this issue, Namas et al. seriously challenge this cytotoxic hypothesis and propose to replace it by a cytokinic approach. In a rodent model of sepsis, these authors elegantly demonstrate that hemoadsorption using a large surface-area polymer could reduce and, more importantly, relocalize and reprogram sepsis-induced acute inflammation, while simultaneously lowering infectious burden and liver damage. Although challenging, this new theory can be considered complementary to the existing cytotoxic hypotheses by coupling reduced endothelial damage at the interstitial level (cytotoxic approach) with the concept of reprogramming leucocytes and mediators toward infected tissue, thus emptying the bloodstream of important promoters of remote organ damages (cytokinic approach).
近三十年来，研究人员一直在致力于从循环系统中清除多余的炎症介质的策略（即“细胞毒性”方法）。使用体外设备的血液净化技术确实可以非特异性地从循环系统中清除多种炎症介质。在动物模型中，这种针对多种介质或多效性的方法已被证明可以下调全身炎症并恢复免疫稳态。在本期杂志中，Namas 等人对这一细胞毒性假说提出了质疑，并提出用细胞因子方法来替代它。在脓毒症的啮齿动物模型中，这些作者巧妙地证明了使用大表面积聚合物的血液吸附可以减少，更重要的是，可以重新定位和重新编程脓毒症引起的急性炎症，同时降低感染负担和肝损伤。虽然具有挑战性，但通过将细胞间水平的内皮损伤降低（细胞毒性方法）与将白细胞和介质重新编程为感染组织的概念相结合，这种新理论可以被认为是对现有的细胞毒性假说的补充，从而清除了血液中重要的远程器官损伤的促进剂（细胞因子方法）。
