Extracorporeal Elimination of Pro- and Anti-inflammatory Modulators by the Cytokine Adsorber CytoSorb® in Patients with Hyperinflammation: A Prospective Study.
Helen Graf, Caroline Gräfe, Mathias Bruegel, Felix L Happich, Vassilissa Wustrow, Aljoscha Wegener, Wolfgang Wilfert, Michael Zoller, Uwe Liebchen, Michael Paal, Christina Scharf
{"title":"Extracorporeal Elimination of Pro- and Anti-inflammatory Modulators by the Cytokine Adsorber CytoSorb<sup>®</sup> in Patients with Hyperinflammation: A Prospective Study.","authors":"Helen Graf, Caroline Gräfe, Mathias Bruegel, Felix L Happich, Vassilissa Wustrow, Aljoscha Wegener, Wolfgang Wilfert, Michael Zoller, Uwe Liebchen, Michael Paal, Christina Scharf","doi":"10.1007/s40121-024-01028-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>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<sup>®</sup> (CS) (adsorption of especially hydrophobic molecules < 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.</p><p><strong>Methods: </strong>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: <math><mrow><mi>b</mi> <mi>l</mi> <mi>o</mi> <mi>o</mi> <mi>d</mi> <mspace></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></mspace> <mfenced><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></mspace> <mfenced><mrow><mi>pre</mi></mrow> </mfenced> </mrow> </mfrac> <mo>.</mo></mrow> </math> 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 < 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 < 0.05) decrease in patients' blood after 12 h was only detected for interleukin 10.</p><p><strong>Conclusions: </strong>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.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov NCT04913298, registration date June 4, 2021.</p>","PeriodicalId":13592,"journal":{"name":"Infectious Diseases and Therapy","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11343926/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Infectious Diseases and Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40121-024-01028-8","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/18 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
Abstract
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 < 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: 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 < 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 < 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.
导言：脓毒症重症患者体内释放的促炎细胞因子会导致内皮功能障碍，造成心循环功能不全。使用细胞因子吸附器 CytoSorb® (CS)（吸附特别疏水分子的方法）可在体外清除这些细胞因子：前瞻性 Cyto-SOLVE 研究包括 15 名患有败血症或其他炎症（白细胞介素 6 > 500 pg/ml）、持续接受肾脏替代治疗并应用 CS 的患者。在 CS 前后以及在预定的时间点测量了患者血液中的各种细胞因子和趋化因子。通过对相关样本进行 Wilcoxon 检验，可检测出浓度的显著变化。吸附剂的清除率（毫升/分钟）计算公式为：b l o o d f l o w ∗ c o n c e n t r a t i o n p r e - p o s t c o n c e n t r a t i o n pre。 结果：安装 CS 后，大多数炎症介质的初始体外清除率高达 70-100 毫升/分钟，治疗 6 小时后迅速降至 10-30 毫升/分钟。促炎细胞因子和抗炎细胞因子的清除率没有差异。尽管有体外吸附作用，但 CS 对促炎细胞因子和抗炎细胞因子的清除率仍有显著差异（p 结论）：CS 既能吸附促炎介质，也能吸附抗炎介质，而且吸附率没有相关差异。吸附器的快速饱和会导致清除率迅速下降。这种非特异性细胞因子吸附的潜在临床益处或危害需要在未来进行评估：试验注册：ClinicalTrials.gov NCT04913298，注册日期：2021年6月4日。
期刊介绍：
Infectious Diseases and Therapy is an international, open access, peer-reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of infectious disease therapies and interventions, including vaccines and devices. Studies relating to diagnostic products and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged.
Areas of focus include, but are not limited to, bacterial and fungal infections, viral infections (including HIV/AIDS and hepatitis), parasitological diseases, tuberculosis and other mycobacterial diseases, vaccinations and other interventions, and drug-resistance, chronic infections, epidemiology and tropical, emergent, pediatric, dermal and sexually-transmitted diseases.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
