• T Eichhorn, S Rauscher, M Gröger, M B Fischer, and V Weber.
• 1CD Laboratory for Innovative Therapy Approaches in Sepsis, Danube University Krems, Krems, Austria 2Core Facility Imaging, Medical University of Vienna, Vienna, Austria.
• Shock. 2015 Oct 1;44 Suppl 2:18.

IntroductionThe crucial role of the endothelium in sepsis is well recognized. The aim of this study was to establish a flow model to study endothelial activation induced by lipopolysaccharide (LPS) or by plasma from septic patients. We report on the application of this model to assess the effect of adsorbent-based cytokine modulation on endothelial activation.MethodsHuman whole blood was stimulated with LPS and the stimulated blood or plasma from septic patients was treated in vitro with a polystyrene-divinylbenzene (PS-DVB) adsorbent (average pore size: 30 nm) at an adsorbent-to-plasma ratio of 1:10 (vol/vol). After adsorption, plasma was diluted tenfold with cell culture medium to yield conditioned medium. Human umbilical vein endothelial cells (HUVEC) cultured at a shear stress of 5 dyn/cm2 in μ-slides (Ibidi, Martinsried, Germany) were stimulated with conditioned media. Endothelial activation was assessed by the release of interleukin (IL)-1β, IL-6, IL-8, IL-10, and tumor necrosis factor (TNF)-α, and by the expression of intercellular adhesion molecule-1 (ICAM-1) and E-selectin. Adhesion of monocytic THP-1 cells to HUVEC was studied at a shear stress of 1 dyn/cm2.ResultsTreatment with the adsorbent substantially decreased cytokine levels in LPS-stimulated blood and septic plasma. HUVEC stimulation with adsorbent-treated plasma resulted in diminished cytokine release, reduced ICAM-1 and E-selectin expression, as well as reduced THP-1 adhesion in comparison to untreated controls (Fig.).ConclusionThe flow model allows to study endothelial activation and the interaction of activated endothelial cells with blood cells. Cytokine modulation with PS-DVB polymers reduced endothelial activation and decreased monocyte adhesion.(Figure is included in full-text article.).

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