Experimental work aimed at the identification of DANGER molecules causing sepsis associated hyperinflammation and endothelial cell damage in vivo. Plasma samples taken before and after Cytosorb ® treatment were tested for their contents in DANGER signaling molecules activating RAGE (receptor for advanced glycation end products) such as  AGEs (advanced glycation end products), oxDNA (oxidized DNA), and the decoy ligand soluble RAGE (sRAGE). Inflammatory markers IL-1β, IL-6, IL-8, and anti-inflammatory IL-10 were also quantified in plasma samples before and after  Cytosorb® treatment. 
Complementary to the analysis of plasma and leukocytes in patients treated with Cytosorb®, the Cytosorb® column of one patient was fractionated and individual fractions were analyzed for their contents in AGEs and oxDNA.  
From RAGE binding DANGER ligands AGEs do not appear to be removed and cannot be retrieved from a Cytosorb® column by protein fractionation procedures. By contrast, the concentrations of oxDNA were found to be significantly diminished in plasma samples of Cytosorb® treated patients; in addition, total DNA as well as oxDNA were detected in most active protein fractions (F#11-F15) of a Cytosorb® column. sRAGE scavenger concentrations were not systematically decreased by Cytosorb®
Conclusion: Circulating oxDNA is a novel stress component removed by Cytosorb®  treatment in patients with sepsis and cardiovascular surgery contributing to the improved inflammatory cytokine and leukocyte adhesion receptor profile. Anti-inflammatory sRAGE and IL-10 are not diminished by Cytosorb®.

02 - Damage molecules: S100, soluble RAGE and oxidized DNA! Removed by Cytosorb® treatment