title: Characterization of Adsorbents for Cytokine Removal from Blood in an In Vitro Model.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  These results confirm the hypothesis that cytokine removal from the blood should approach physiological levels in order to reduce endothelial cell activation.
authors.affiliation: 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.
authors.forename: Stephan
authors.identifier: 0000-0003-1944-9898
authors.initials: S
authors.lastname: Harm
authors.affiliation: Department of Pharmaceutical Technology and Biopharmaceutics, University of Vienna, Althanstraße 14, 1090 Vienna, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Gabor
authors.affiliation: Department for Health Sciences and Biomedicine, Danube University Krems, Dr.-Karl-Dorrek-Straße 30, 3500 Krems, Austria.
authors.forename: Jens
authors.initials: J
authors.lastname: Hartmann
mesh_terms: D019040:E-Selectin / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000302:isolation & purification* / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification* / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008954:Models, Biological; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011137:Polystyrenes / Q000737:chemistry*; D016060:Sorption Detoxification / Q000295:instrumentation; D014409:Tumor Necrosis Factor-alpha / Q000302:isolation & purification* / Q000494:pharmacology; D014753:Vinyl Compounds / Q000737:chemistry
chemical_list: C552102:Amberchrom CG161 M; D019040:E-Selectin; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D011108:Polymers; D011137:Polystyrenes; C546936:SELE protein, human; D014409:Tumor Necrosis Factor-alpha; D014753:Vinyl Compounds; D018799:Intercellular Adhesion Molecule-1; C004985:divinyl benzene