Department for Health Sciences and Biomedicine, Danube University Krems, Dr.-Karl-Dorrek-Straße 30, 3500 Krems, Austria; Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
J Immunol Res. 2015;2015:484736. doi: 10.1155/2015/484736. Epub 2015 Dec 7.
Cytokines are basic targets that have to be removed effectively in order to improve the patient's health status in treating severe inflammation, sepsis, and septic shock. Although there are different adsorbents commercially available, the success of their clinical use is limited. Here, we tested different adsorbents for their effective removal of cytokines from plasma and the resulting effect on endothelial cell activation.
The three polystyrene divinylbenzene (PS-DVB) based adsorbents Amberchrom CG161c and CG300m and a clinically approved haemoperfusion adsorbent (HAC) were studied with regard to cytokine removal in human blood. To induce cytokine release from leucocytes, human blood cells were stimulated with 1 ng/ml LPS for 4 hours. Plasma was separated and adsorption experiments in a dynamic model were performed. The effect of cytokine removal on endothelial cell activation was evaluated using a HUVEC-based cell culture model. The beneficial outcome was assessed by measuring ICAM-1, E-selectin, and secreted cytokines IL-8 and IL-6. Additionally the threshold concentration for HUVEC activation by TNF-α and IL-1β was determined using this cell culture model.
CG161c showed promising results in removing the investigated cytokines. Due to its pore size the adsorbent efficiently removed the key factor TNF-α, outperforming the commercially available adsorbents. The CG161c treatment reduced cytokine secretion and expression of cell adhesion molecules by HUVEC which underlines the importance of effective removal of TNF-α in inflammatory diseases.
These results confirm the hypothesis that cytokine removal from the blood should approach physiological levels in order to reduce endothelial cell activation.
细胞因子是基本靶点，为了改善严重炎症、脓毒症和感染性休克患者的健康状况，必须有效地将其清除。虽然有不同的商业吸附剂可用，但它们的临床应用效果有限。在这里，我们测试了不同的吸附剂，以有效去除血浆中的细胞因子，并研究其对内皮细胞激活的影响。
研究了三种基于聚苯乙烯二乙烯基苯（PS-DVB）的吸附剂 Amberchrom CG161c 和 CG300m 以及一种临床批准的血液灌流吸附剂（HAC），以研究它们在人血中去除细胞因子的能力。为了诱导白细胞释放细胞因子，用 1ng/ml LPS 刺激人血细胞 4 小时。分离血浆并在动态模型中进行吸附实验。通过基于 HUVEC 的细胞培养模型评估细胞因子去除对内皮细胞激活的影响。通过测量 ICAM-1、E-选择素以及分泌细胞因子 IL-8 和 IL-6 来评估有益的结果。此外，还使用该细胞培养模型确定了 TNF-α 和 IL-1β 激活 HUVEC 的阈值浓度。
CG161c 在去除研究中的细胞因子方面表现出良好的效果。由于其孔径大小，该吸附剂有效地去除了关键因子 TNF-α，优于市售的吸附剂。CG161c 处理减少了细胞因子的分泌和细胞黏附分子的表达，这强调了在炎症性疾病中有效去除 TNF-α 的重要性。
这些结果证实了这样一种假设，即从血液中去除细胞因子应接近生理水平，以减少内皮细胞的激活。
