Harm Stephan, Falkenhagen Dieter, Hartmann Jens
Department for Health Sciences and Biomedicine, Danube University Krems, Krems - Austria.
Int J Artif Organs. 2014 Mar;37(3):222-32. doi: 10.5301/ijao.5000304. Epub 2014 Apr 4.
Lipopolysaccharides (LPS) are extremely strong stimulators of inflammatory reactions, act at very low concentrations, and are involved in the pathogenesis of sepsis and septic shock. Because of its toxicity, the efficient removal of endotoxin from patients' blood is very important in clinical medicine. The purpose of this study was to determine the endotoxin adsorption capacities of commercial endotoxin adsorbers for endotoxin removal in buffer solution, protein solution, serum and heparinized plasma; some of these were also characterized in whole blood. The tested LPS adsorbers were Toraymyxin® PMX-20R, Alteco® LPS Adsorber, DEAE-Sepharose, Polymyxin B-Agarose, and EndoTrap® red.
The adsorber materials were tested in buffer and protein solutions spiked with fluorescently labeled LPS (100 ng/ml). Additionally, batch tests with LPS-spiked serum, heparinized plasma and whole blood were performed with an LPS concentration of 5 ng/ml. Additionally, the washing solutions of the two tested Polymyxin B (PMB)-based adsorbers were analyzed for PMB release to determine if the resulting LPS inactivation was caused by PMB leakage.
The results show that DEAE-Sepharose was most effective in LPS adsorption. Of the other tested endotoxin removal materials, only the PMB-based adsorbers were able to reduce the LPS activity. However, we were able to show that the reduction in LPS activity was caused by desorbed PMB, which inactivates endotoxins.
None of the adsorbents that were tested in this study showed promising results for potential use in extracorporeal blood purification.
脂多糖（LPS）是炎症反应的极强刺激物，在极低浓度下即可发挥作用，并参与脓毒症和脓毒性休克的发病机制。由于其毒性，在临床医学中从患者血液中有效去除内毒素非常重要。本研究的目的是测定市售内毒素吸附剂在缓冲溶液、蛋白质溶液、血清和肝素化血浆中去除内毒素的吸附能力；其中一些还在全血中进行了特性分析。所测试的LPS吸附剂包括Toraymyxin® PMX - 20R、Alteco® LPS吸附剂、二乙氨基乙基琼脂糖（DEAE - Sepharose）、多粘菌素B - 琼脂糖（Polymyxin B - Agarose）和EndoTrap® red。
将吸附剂材料在添加了荧光标记LPS（100 ng/ml）的缓冲溶液和蛋白质溶液中进行测试。此外，还对添加了LPS（浓度为5 ng/ml）的血清、肝素化血浆和全血进行了批量测试。另外，对两种测试的基于多粘菌素B（PMB）的吸附剂的洗涤液进行分析，以确定PMB的释放情况，从而判断由此导致的LPS失活是否是由PMB泄漏引起的。
结果表明，DEAE - Sepharose在LPS吸附方面最为有效。在其他测试的内毒素去除材料中，只有基于PMB的吸附剂能够降低LPS活性。然而，我们能够证明LPS活性的降低是由解吸的PMB引起的，PMB可使内毒素失活。
本研究中测试的吸附剂均未显示出在体外血液净化中具有潜在应用的良好前景。
