Extracorporeal Elimination of Pro- and Anti-inflammatory Modulators by the Cytokine Adsorber CytoSorb®in Patients with Hyperinflammation: A Prospective Study

Introduction: The release of pro-inflammatory cytokines in critically ill patients with sepsis leads to endothelial dysfunction resulting in cardiocirculatory insufficiency. Their extracorporeal elimination using the cytokine adsorber CytoSorb^®(CS) (adsorption of especially hydrophobic molecules &lt; 60 kDa) might be promising, but data about the adsorption capacity as well as a potential harmful adsorption of anti-inflammatory cytokines are missing so far. Methods: The prospective Cyto-SOLVE-study included 15 patients with sepsis or other hyperinflammatory conditions (interleukin 6 > 500 pg/ml), continuous kidney replacement therapy, and the application of CS. Various cytokines and chemokines were measured pre- and post-CS as well as in patients’ blood at predefined timepoints. Significant changes in the concentrations were detected with the Wilcoxon test with associated samples. Clearance of the adsorber (ml/min) was calculated with: <inline-formula id="IEq1"><alternatives><math><mrow><mi>b</mi><mi>l</mi><mi>o</mi><mi>o</mi><mi>d</mi><mspace width="0.166667em"></mspace><mi>f</mi><mi>l</mi><mi>o</mi><mi>w</mi><mrow></mrow><mo>∗</mo><mfrac><mrow><mi>c</mi><mi>o</mi><mi>n</mi><mi>c</mi><mi>e</mi><mi>n</mi><mi>t</mi><mi>r</mi><mi>a</mi><mi>t</mi><mi>i</mi><mi>o</mi><mi>n</mi><mspace width="0.166667em"></mspace><mfenced close=")" open="("><mrow><mi>p</mi><mi>r</mi><mi>e</mi><mo>-</mo><mi>p</mi><mi>o</mi><mi>s</mi><mi>t</mi></mrow></mfenced></mrow><mrow><mi>c</mi><mi>o</mi><mi>n</mi><mi>c</mi><mi>e</mi><mi>n</mi><mi>t</mi><mi>r</mi><mi>a</mi><mi>t</mi><mi>i</mi><mi>o</mi><mi>n</mi><mspace width="0.166667em"></mspace><mfenced close=")" open="("><mrow><mi mathvariant="italic">pre</mi></mrow></mfenced></mrow></mfrac><mo>.</mo></mrow></math><tex-math id="IEq1_TeX">\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$blood\,flow*\frac{{concentration\, \left( {pre - post} \right)}}{{concentration\, \left( {pre} \right)}}.$$\end{document}</tex-math><inline-graphic href="40121_2024_1028_Article_IEq1.gif"></inline-graphic></alternatives></inline-formula> Results: Most of the inflammatory mediators showed a high initial extracorporeal clearance of 70–100 ml/min after CS installation, which dropped quickly to 10-30 ml/min after 6 h of treatment. No difference in clearance was observed between pro- and anti-inflammatory cytokines. Despite extracorporeal adsorption, a significant (p&lt; 0.05) decrease in the blood concentration after 6 h was only observed for the pro-inflammatory cytokines tumor necrosis factorα (TNF-α) (median 284 vs. 230 pg/ml), vascular endothelial growth factor (VEGF) (median 294 vs. 252 pg/ml), macrophage inflammatory protein 1a (MIP-1a) (median 11.1 vs. 9.0 pg/ml), and regulated upon activation, normal T cell expressed and secreted (RANTES) (median 811 vs. 487 pg/ml) as well as the anti-inflammatory cytokines interleukin 4 (median 9.3 vs. 6.4 pg/ml), interleukin 10 (median 88 vs. 56 pg/ml), and platelet-derived growth factor (PDGF) (median 177 vs. 104 pg/ml). A significant (p&lt; 0.05) decrease in patients’ blood after 12 h was only detected for interleukin 10. Conclusions: CS can adsorb pro- as well as anti-inflammatory mediators with no relevant difference regarding the adsorption rate. A fast saturation of the adsorber resulted in a rapid decrease of the clearance. The potential clinical benefit or harm of this unspecific cytokine adsorption needs to be evaluated in the future. Trial Registration: ClinicalTrials.gov NCT04913298, registration date June 4, 2021.