Center for Molecular Medicine, University of Amsterdam, Amsterdam, The Netherlands.
J Innate Immun. 2010;2(5):422-30. doi: 10.1159/000316286. Epub 2010 Jun 8.
The systemic inflammatory response syndrome (SIRS) is the predominantly cytokine-mediated, pro-inflammatory response of the host to invading pathogens and is considered the hallmark sign of sepsis. Molecular components of this response can be divided into cytokines, plasma cascades and acute phase proteins while the predominant cellular components are leukocytes and the endothelium. High-throughput genetic profiling studies have led to increased insights into leukocyte regulation during sepsis. New players in the pro-inflammatory cytokine network include interleukin-17, high-mobility group box-1 protein, macrophage migration inhibitory factor, the myeloid-related proteins Mrp8 and Mrp14, and soluble triggering receptor expressed on myeloid cells-1. Activation of coagulation with concurrent downregulation of anticoagulant systems and fibrinolysis are almost universally present in septic patients with SIRS. Increasing evidence points to an extensive cross-talk between inflammation and coagulation, in which the protease-activated cell receptors play an important role. Sepsis causes excessive activation of the complement system in which C5a plays a key part. Further dissection of the role of host-pathogen interactions, the cytokine network, the coagulation cascade, the complement system and their multidirectional interactions in sepsis will pave the way for new treatment targets that can modify the excessive and collective activation of all these systems.
全身炎症反应综合征（SIRS）是宿主对入侵病原体的主要以细胞因子介导的促炎反应，被认为是脓毒症的标志性特征。该反应的分子成分可分为细胞因子、血浆级联和急性期蛋白，而主要的细胞成分是白细胞和内皮细胞。高通量基因谱研究增加了对脓毒症期间白细胞调节的深入了解。促炎细胞因子网络中的新成员包括白细胞介素-17、高迁移率族蛋白-1 蛋白、巨噬细胞移动抑制因子、髓系相关蛋白 Mrp8 和 Mrp14 以及骨髓细胞表达的可溶性触发受体-1。在发生 SIRS 的脓毒症患者中，几乎普遍存在凝血激活同时抗凝系统和纤溶下调的现象。越来越多的证据表明炎症和凝血之间存在广泛的相互作用，其中蛋白酶激活的细胞受体起着重要作用。脓毒症会导致补体系统过度激活，其中 C5a 起着关键作用。进一步剖析宿主-病原体相互作用、细胞因子网络、凝血级联、补体系统及其在脓毒症中的多向相互作用，将为能够改变所有这些系统过度和集体激活的新治疗靶点铺平道路。
