Hemoadsorption Reprograms Inflammation in Experimental Gram-negative Septic Peritonitis: Insights from In Vivo and In Silico Studies
Hemoadsorption Reprograms Inflammation in Experimental Gram-negative Septic Peritonitis: Insights from In Vivo and In Silico Studies
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DOI：
10.2119/molmed.2012.00106
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发表时间：
2012-10-01
影响因子：
5.7
通讯作者：
Vodovotz, Yoram
中科院分区：
文献类型：
--
作者：
Namas, Rami A.;Namas, Rajaie;Vodovotz, Yoram
炎症反应的不适当区室化导致脓毒症中的全身性炎症。血液吸附（HA）是一种新兴的方法来调节脓毒症引起的炎症。我们试图确定HA对大肠杆菌诱导的纤维蛋白性腹膜炎大鼠炎症细胞的影响。假设：HA在脓毒症中重新编程和重新区室化炎症。Sprague道利雄性大鼠用E.大肠杆菌腹膜炎，24小时后，随机分为HA组或假治疗组（仅脓毒症）。测定在0、1、3和6 h（即，总实验性脓毒症的24-30 h）采集的静脉血样品和在0和6 h采集的腹膜样品的14种细胞因子沿着NO2-/NO3-。在0和6 h评估腹膜液中的细菌计数。与假手术组相比，HA组血浆肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、CXCL-1和CCL 2显著降低。主成分分析（PCA）表明，假手术中的炎症由IL-6和TNF-α驱动，而HA相关炎症主要由TNF-α、CXCL-1、IL-10和CCL 2驱动。HA组与假手术组相比，腹膜细菌计数、血浆天冬氨酸转氨酶水平和腹膜IL-5、IL-6、IL-18、干扰素（IFN）-γ和NO2-/NO3-均显著降低，而CXCL-1和CCL 2以及TNF-α、CXCL-1和CCL 2的腹膜/血浆比值显著升高，表明HA诱导的炎症重新区室化导致不同的炎症驱动因子，其部分由PCA识别。总之，本研究证明了结合体内/计算机模拟方法的实用性，并表明HA对局部和全身隔室之间的介质梯度产生差异效应，最终使宿主受益。在线地址：http://www.molmed.org doi：10.2119/molmed.2012.00106
Improper compartmentalization of the inflammatory response leads to systemic inflammation in sepsis. Hemoadsorption (HA) is an emerging approach to modulate sepsis-induced inflammation. We sought to define the effects of HA on inflammatory cornpartmentalization in Escherichia coli-induced fibrin peritonitis in rats. Hypothesis: HA both reprograms and recompartmentalizes inflammation in sepsis. Sprague Dawley male rats were subjected to E. coli peritonitis and, after 24 h, were randomized to HA or sham treatment (sepsis alone). Venous blood samples collected at 0, 1, 3 and 6 h (that is, 24-30 h of total experimental sepsis), and peritoneal samples collected at 0 and 6 h, were assayed for 14 cytokines along with NO2-/NO3-. Bacterial counts were assessed in the peritoneal fluid at 0 and 6 h. Plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, CXCL-1, and CCL2 were significantly reduced in HA versus sham. Principal component analysis (PCA) suggested that inflammation in sham was driven by IL-6 and TNF-alpha, whereas HA-associated inflammation was driven primarily by TNF-alpha, CXCL-1, IL-10 and CCL2. Whereas peritoneal bacterial counts, plasma aspartate transaminase levels and peritoneal IL-5, IL-6, IL-18, interferon (IFN)-gamma and NO2-/NO3- were significantly lower, both CXCL-1 and CCL2 as well as the peritoneal-to-plasma ratios of TNF-alpha, CXCL-1 and CCL2 were significantly higher in HA versus sham, suggesting that HA-induced inflammatory recompartmentalization leads to the different inflammatory drivers discerned in part by PCA. In conclusion, this study demonstrates the utility of combined in vivo/in silico methods and suggests that HA exerts differential effects on mediator gradients between local and systemic compartments that ultimately benefit the host. Online address: http://www.molmed.org doi: 10.2119/molmed.2012.00106