INF/IR-9: IN VITRO CHARACTERIZATION OF A NEW ADSORBENT FOR CYTOKINES IN EXTRACORPOREAL BLOOD PURIFICATION.

INTRODUCTION: For the treatment of severe inflammation, sepsis and septic shock by membrane-adsorption based extracorporeal blood purification technologies, cytokines are basic targets that have to be removed effectively in order to improve the patient's health status. Although there are different adsorbents commercially available, the success of their clinical use is limited. In order to suppress systemic effects in these disease patterns, effective removal of cytokines below a critical threshold is necessary.

METHODS: Polystyrene divinylbenzene based adsorbents Amberchrom® CG161c, CG300m and a clinical approved haemoperfusion adsorbent for cytokine removal were studied with regard to cytokine removal in human blood. To induce an overproduction of cytokine release, human blood cells were stimulated with 1 ng/ml LPS (E. coli) for 4 hours. The plasma, including the inflammatory mediators, was separated and adsorption experiments in a dynamic model were performed. The effect of cytokine removal on endothelial cell activation was evaluated using a cell culture model with HUVEC. The beneficial outcome was assessed by measuring ICAM-1, E-selectin and the secreted cytokines IL-8 and IL-6. Additionally the threshold concentration for HUVEC activation by TNF-α and IL-1β was determined using a cell culture model.

RESULTS: The adsorbent CG161c shows promising results in removing the investigated cytokines. Furthermore, the CG161c treatment caused reduced cytokine secretion and expression of cell adhesion molecules by HUVEC which emphasizes the importance of effective removal of TNF-α in inflammatory diseases.

CONCLUSION: These results confirm the assumption, that cytokine removal from the blood should approach physiological levels in order to prevent endothelial cell activation.