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Cefiderocol Protects against Cytokine- and Endotoxin-Induced Disruption of Vascular Endothelial Cell Integrity in an In Vitro Experimental Model

The severe course of bloodstream infections with Gram-negative bacilli can lead to organ dysfunctions and compromise the integrity of the vascular barrier, which are the hallmarks of sepsis. This study aimed to investigate the potential effect of cefiderocol on the barrier function of vascular endot...

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Autores principales: Hildebrand, Dagmar, Böhringer, Jana, Körner, Eva, Chiriac, Ute, Förmer, Sandra, Sähr, Aline, Hoppe-Tichy, Torsten, Heeg, Klaus, Nurjadi, Dennis
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137736/
https://www.ncbi.nlm.nih.gov/pubmed/35625225
http://dx.doi.org/10.3390/antibiotics11050581
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author Hildebrand, Dagmar
Böhringer, Jana
Körner, Eva
Chiriac, Ute
Förmer, Sandra
Sähr, Aline
Hoppe-Tichy, Torsten
Heeg, Klaus
Nurjadi, Dennis
author_facet Hildebrand, Dagmar
Böhringer, Jana
Körner, Eva
Chiriac, Ute
Förmer, Sandra
Sähr, Aline
Hoppe-Tichy, Torsten
Heeg, Klaus
Nurjadi, Dennis
author_sort Hildebrand, Dagmar
collection PubMed
description The severe course of bloodstream infections with Gram-negative bacilli can lead to organ dysfunctions and compromise the integrity of the vascular barrier, which are the hallmarks of sepsis. This study aimed to investigate the potential effect of cefiderocol on the barrier function of vascular endothelial cells (vECs) in an in vitro experimental set-up. Human umbilical vein cells (HUVECs), co-cultured with erythrocyte-depleted whole blood for up to 48 h, were activated with tumor necrosis factor-alpha (TNF-α) or lipopolysaccharide (LPS) to induce endothelial damage in the absence or presence of cefiderocol (concentrations of 10, 40 and 70 mg/L). The endothelial integrity was quantified using transendothelial electrical resistance (TEER) measurement, performed at 0, 3, 24 and 48 h after stimulation. Stimulation with TNF-α and LPS increased the endothelial permeability assessed by TEER at 24 and 48 h of co-culture. Furthermore, cefiderocol reduces interleukin-6 (IL-6), interleukin-1β (IL-1β) and TNF-α release in peripheral blood mononuclear cells (PBMCs) following LPS stimulation in a dose-dependent manner. Collectively, the data suggest that cefiderocol may have an influence on the cellular immune response and might support the maintenance of vEC integrity during inflammation associated with infection with Gram-negative bacteria, which warrants further investigations.
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spelling pubmed-91377362022-05-28 Cefiderocol Protects against Cytokine- and Endotoxin-Induced Disruption of Vascular Endothelial Cell Integrity in an In Vitro Experimental Model Hildebrand, Dagmar Böhringer, Jana Körner, Eva Chiriac, Ute Förmer, Sandra Sähr, Aline Hoppe-Tichy, Torsten Heeg, Klaus Nurjadi, Dennis Antibiotics (Basel) Communication The severe course of bloodstream infections with Gram-negative bacilli can lead to organ dysfunctions and compromise the integrity of the vascular barrier, which are the hallmarks of sepsis. This study aimed to investigate the potential effect of cefiderocol on the barrier function of vascular endothelial cells (vECs) in an in vitro experimental set-up. Human umbilical vein cells (HUVECs), co-cultured with erythrocyte-depleted whole blood for up to 48 h, were activated with tumor necrosis factor-alpha (TNF-α) or lipopolysaccharide (LPS) to induce endothelial damage in the absence or presence of cefiderocol (concentrations of 10, 40 and 70 mg/L). The endothelial integrity was quantified using transendothelial electrical resistance (TEER) measurement, performed at 0, 3, 24 and 48 h after stimulation. Stimulation with TNF-α and LPS increased the endothelial permeability assessed by TEER at 24 and 48 h of co-culture. Furthermore, cefiderocol reduces interleukin-6 (IL-6), interleukin-1β (IL-1β) and TNF-α release in peripheral blood mononuclear cells (PBMCs) following LPS stimulation in a dose-dependent manner. Collectively, the data suggest that cefiderocol may have an influence on the cellular immune response and might support the maintenance of vEC integrity during inflammation associated with infection with Gram-negative bacteria, which warrants further investigations. MDPI 2022-04-26 /pmc/articles/PMC9137736/ /pubmed/35625225 http://dx.doi.org/10.3390/antibiotics11050581 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Communication
Hildebrand, Dagmar
Böhringer, Jana
Körner, Eva
Chiriac, Ute
Förmer, Sandra
Sähr, Aline
Hoppe-Tichy, Torsten
Heeg, Klaus
Nurjadi, Dennis
Cefiderocol Protects against Cytokine- and Endotoxin-Induced Disruption of Vascular Endothelial Cell Integrity in an In Vitro Experimental Model
title Cefiderocol Protects against Cytokine- and Endotoxin-Induced Disruption of Vascular Endothelial Cell Integrity in an In Vitro Experimental Model
title_full Cefiderocol Protects against Cytokine- and Endotoxin-Induced Disruption of Vascular Endothelial Cell Integrity in an In Vitro Experimental Model
title_fullStr Cefiderocol Protects against Cytokine- and Endotoxin-Induced Disruption of Vascular Endothelial Cell Integrity in an In Vitro Experimental Model
title_full_unstemmed Cefiderocol Protects against Cytokine- and Endotoxin-Induced Disruption of Vascular Endothelial Cell Integrity in an In Vitro Experimental Model
title_short Cefiderocol Protects against Cytokine- and Endotoxin-Induced Disruption of Vascular Endothelial Cell Integrity in an In Vitro Experimental Model
title_sort cefiderocol protects against cytokine- and endotoxin-induced disruption of vascular endothelial cell integrity in an in vitro experimental model
topic Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137736/
https://www.ncbi.nlm.nih.gov/pubmed/35625225
http://dx.doi.org/10.3390/antibiotics11050581
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