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. 2023 Mar 21;27(1):117.
doi: 10.1186/s13054-023-04391-z.

CytoSorb hemoperfusion markedly attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo

Aron Jansen  1   2 , Nicole J B Waalders #  3   4 , Dirk P T van Lier #  3   4 , Matthijs Kox  3   4 , Peter Pickkers  5   6
Affiliations

CytoSorb hemoperfusion markedly attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo

Aron Jansen et al. Crit Care. .

Abstract

Background: The CytoSorb hemoadsorption device has been demonstrated to be capable of clearing inflammatory cytokines, but has not yet been shown to attenuate plasma cytokine concentrations. We investigated the effects of CytoSorb hemoperfusion on plasma levels of various cytokines using the repeated human experimental endotoxemia model, a highly standardized and reproducible human in vivo model of systemic inflammation and immunological tolerance induced by administration of bacterial lipopolysaccharide (LPS).

Methods: Twenty-four healthy male volunteers (age 18-35) were intravenously challenged with LPS (a bolus of 1 ng/kg followed by continuous infusion of 0.5 ng/kg/hr for three hours) twice: on day 0 to quantify the initial cytokine response and on day 7 to quantify the degree of endotoxin tolerance. Subjects either received CytoSorb hemoperfusion during the first LPS challenge (CytoSorb group), or no intervention (control group). Plasma cytokine concentrations and clearance rates were determined serially. This study was registered at ClinicalTrials.gov (NCT04643639, date of registration November 24th 2020).

Results: LPS administration led to a profound increase in plasma cytokine concentrations during both LPS challenge days. Compared to the control group, significantly lower plasma levels of tumor necrosis factor (TNF, - 58%, p < 0.0001), interleukin (IL)-6 ( - 71%, p = 0.003), IL-8 ( - 48%, p = 0.02) and IL-10 ( - 26%, p = 0.03) were observed in the CytoSorb group during the first LPS challenge. No differences in cytokine responses were observed during the second LPS challenge.

Conclusions: CytoSorb hemoperfusion effectively attenuates circulating cytokine concentrations during systemic inflammation in humans in vivo, whereas it does not affect long-term immune function. Therefore, CytoSorb therapy may be of benefit in conditions characterized by excessive cytokine release.

Keywords: CytoSorb; Cytokines; Extracorporeal therapy; Hemoadsorption; Sepsis; Systemic inflammation.

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Conflict of interest statement

The authors have no competing interest to declare.

Figures

Fig. 1
Fig. 1
Schematic overview of study procedures. LPS = lipopolysaccharide; ASA = acetylsalicylic acid; ACT = activated clotting time
Fig. 2
Fig. 2
Plasma concentrations of A TNF, B IL-6, C IL-8 and D IL-10 during the first (D0) and second (D7) LPS challenge day. Data are displayed as median (line) and interquartile range (shaded area). P values were computed using two-way repeated measures analysis of variance (time × group interaction term). D0 = day 0, D7 = day 7, TNF = tumor necrosis factor, IL = interleukin
Fig. 3
Fig. 3
Plasma concentrations measured at the inlet and outlet ports of the adsorber (left panels), clearance rates (center panels) and elimination rates (right panels) of A TNF, B IL-6, C IL-8 and D IL-10 during the first LPS challenge day in the CytoSorb group. Data are displayed as median (line) and interquartile range (shaded area). TNF = tumor necrosis factor, IL = interleukin
Fig. 4
Fig. 4
Clinical parameters during the first (D0) and second (D7) LPS challenge. A Mean arterial pressure, B heart rate, C temperature, and D symptom score. Data in panels A, B, and D are displayed as median (line) and interquartile range (shaded area), whereas data in panel C are displayed as mean and standard error of the mean. P values were computed using two-way repeated measures analysis of variance (time × group interaction term). D0 = day 0, D7 = day 7, NRS = numeric rating scale
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Comment in

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