The Effect of Three Different Miniaturized Blood Purification Devices on Plasma Cytokine Concentration in an Ex Vivo Model of Endotoxinemia

Abstract

A novel type of adsorptive plasma filtering device (ETX-A) capable of removing endotoxin from blood in a single step has recently been developed using nanotechnology. In a miniaturized, ex vivo model of extracorporeal circuits, we tested the capacity to reduce plasma cytokine concentration of ETX-A filters in comparison to standard high-flux (HF) filters, high cut-off (HCO) filters and a control. Blood from six healthy volunteers was spiked with endotoxin and then circulated through closed (ETX-A, control) or open (HF, HCO) circuits. Blood flow was set at 16 ml/min and filtration flow at 1 ml/min. Samples for measurement of IL-1ra and IL-6 were taken at baseline and at 4 hours. Compared to control (703.3 [850.6] pg/mL), in HCO (383.5 [1144.1] pg/mL) and ETX-A (490.1 [683.2] pg/mL) filters, plasma IL-1ra pooled pre- and postfilter concentrations were lower at the end of the experiment (P=0.002; P=0.050, respectively) whereas, in standard HF filters, IL-1ra concentration was higher than control. HCO showed a trend toward a reduced relative increase in IL-6 concentration from commencement to end of experiment compared to control (P=0.07). After pooling end-of-experiment plasma cytokine values of novel blood purification devices, we found HCO + ETX-A superior to H with regard to reduction of IL-1ra (-27.0 [-20.5]% vs. 8.1 [18.9]%; p<0.001) and IL-6 (-18.0 [38.3]% vs. -1.1 [24.3]%; P=0.050) compared to control. HCO and ETX-A appeared to significantly reduce plasma IL-1ra and, when combined, plasma IL-6 concentration as well. It appears desirable to manufacture full-size blood purification devices using this technology and to explore their effect on cytokine removal.