Gruda Maryann C, Ruggeberg Karl-Gustav, O'Sullivan Pamela, Guliashvili Tamaz, Scheirer Andrew R, Golobish Thomas D, Capponi Vincent J, Chan Phillip P
CytoSorbents Corporation, Monmouth Junction, New Jersey, United States of America.
PLoS One. 2018 Jan 25;13(1):e0191676. doi: 10.1371/journal.pone.0191676. eCollection 2018.
Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. In sepsis and septic shock, pathogen-associated molecular pattern molecules (PAMPS), such as bacterial exotoxins, cause direct cellular damage and/or trigger an immune response in the host often leading to excessive cytokine production, a maladaptive systemic inflammatory response syndrome response (SIRS), and tissue damage that releases DAMPs, such as activated complement and HMGB-1, into the bloodstream causing further organ injury. Cytokine reduction using extracorporeal blood filtration has been correlated with improvement in survival and clinical outcomes in experimental studies and clinical reports, but the ability of this technology to reduce a broader range of inflammatory mediators has not been well-described. This study quantifies the size-selective adsorption of a wide range of sepsis-related inflammatory bacterial and fungal PAMPs, DAMPs and cytokines, in a single compartment, in vitro whole blood recirculation system.
Purified proteins were added to whole blood at clinically relevant concentrations and recirculated through a device filled with CytoSorb® hemoadsorbent polymer beads (CytoSorbents Corporation, USA) or control (no bead) device in vitro. Except for the TNF-α trimer, hemoadsorption through porous polymer bead devices reduced the levels of a broad spectrum of cytokines, DAMPS, PAMPS and mycotoxins by more than 50 percent.
This study demonstrates that CytoSorb® hemoadsorbent polymer beads efficiently remove a broad spectrum of toxic PAMPS and DAMPS from blood providing an additional means of reducing the uncontrolled inflammatory cascade that contributes to a maladaptive SIRS response, organ dysfunction and death in patients with a broad range of life-threatening inflammatory conditions such as sepsis, toxic shock syndrome, necrotizing fasciitis, and other severe inflammatory conditions.
脓毒症被定义为由宿主对感染的失调反应引起的危及生命的器官功能障碍。在脓毒症和脓毒性休克中，病原体相关分子模式分子（PAMPs），如细菌外毒素，会导致直接的细胞损伤和/或触发宿主的免疫反应，常常导致细胞因子过度产生、适应性不良的全身炎症反应综合征（SIRS）以及组织损伤，从而将如活化补体和高迁移率族蛋白B1（HMGB-1）等损伤相关分子模式（DAMPs）释放到血液中，进而导致进一步的器官损伤。在实验研究和临床报告中，使用体外血液滤过降低细胞因子水平与生存率和临床结局的改善相关，但该技术降低更广泛范围炎症介质的能力尚未得到充分描述。本研究在体外单腔全血再循环系统中，对多种脓毒症相关的炎症性细菌和真菌PAMPs、DAMPs及细胞因子进行了尺寸选择性吸附定量分析。
将纯化蛋白以临床相关浓度添加到全血中，并在体外通过填充有CytoSorb®血液吸附聚合物珠（美国CytoSorbents公司）的装置或对照（无珠）装置进行再循环。除肿瘤坏死因子-α三聚体外，通过多孔聚合物珠装置进行血液吸附可使多种细胞因子、DAMPs、PAMPs和霉菌毒素的水平降低超过50%。
本研究表明，CytoSorb®血液吸附聚合物珠可有效从血液中清除多种有毒的PAMPs和DAMPs，为减少导致适应性不良的SIRS反应、器官功能障碍和死亡的失控炎症级联反应提供了额外手段，这些情况发生在患有多种危及生命的炎症性疾病的患者中，如脓毒症、中毒性休克综合征、坏死性筋膜炎和其他严重炎症性疾病。
