The effect of three different miniaturized blood purification devices on plasma cytokine concentration in an ex vivo model of endotoxinemia.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Haase
M
M
Intensive Care Research, Austin Health, University of Melbourne, Australia.
Bellomo
R
R
Baldwin
I
I
Haase-Fielitz
A
A
Storr
M
M
Krause
B
B
Boyce
N
N
Svobodova
S
S
Li
W
W
Bagshaw
S M
SM
Warrillow
S
S
Langenberg
C
C
Morgera
S
S
D000328:Adult; D019446:Endotoxemia / Q000276:immunology / Q000628:therapy*; D004867:Equipment Design; D006440:Hemofiltration / Q000295:instrumentation*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008070:Lipopolysaccharides / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008904:Miniaturization; D013997:Time Factors
C507763:IL1RN protein, human; C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; C433788:lipopolysaccharide, E. coli O26-B6