Characterization of Adsorbents for Cytokine Removal from Blood in an In Vitro ModelReport as inadecuate




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Journal of Immunology Research - Volume 2015 2015, Article ID 484736, 11 pages -

Research Article

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

Received 31 August 2015; Revised 5 November 2015; Accepted 10 November 2015

Academic Editor: Lenin Pavon

Copyright © 2015 Stephan Harm et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Introduction. 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. Methods. 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. Results. 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. Conclusion. These results confirm the hypothesis that cytokine removal from the blood should approach physiological levels in order to reduce endothelial cell activation.





Author: Stephan Harm, Franz Gabor, and Jens Hartmann

Source: https://www.hindawi.com/



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