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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/5/581 |
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| author | Dagmar Hildebrand Jana Böhringer Eva Körner Ute Chiriac Sandra Förmer Aline Sähr Torsten Hoppe-Tichy Klaus Heeg Dennis Nurjadi |
| author_facet | Dagmar Hildebrand Jana Böhringer Eva Körner Ute Chiriac Sandra Förmer Aline Sähr Torsten Hoppe-Tichy Klaus Heeg Dennis Nurjadi |
| author_sort | Dagmar Hildebrand |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T03:28:09Z |
| format | Article |
| id | doaj.art-45666f82f8fb495bbc843ac52f7f04c2 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T03:28:09Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-45666f82f8fb495bbc843ac52f7f04c22023-11-23T09:48:06ZengMDPI AGAntibiotics2079-63822022-04-0111558110.3390/antibiotics11050581Cefiderocol Protects against Cytokine- and Endotoxin-Induced Disruption of Vascular Endothelial Cell Integrity in an In Vitro Experimental ModelDagmar Hildebrand0Jana Böhringer1Eva Körner2Ute Chiriac3Sandra Förmer4Aline Sähr5Torsten Hoppe-Tichy6Klaus Heeg7Dennis Nurjadi8Medical Microbiology and Hygiene, Department of Infectious Diseases, Heidelberg University Hospital, 69120 Heidelberg, GermanyMedical Microbiology and Hygiene, Department of Infectious Diseases, Heidelberg University Hospital, 69120 Heidelberg, GermanyMedical Microbiology and Hygiene, Department of Infectious Diseases, Heidelberg University Hospital, 69120 Heidelberg, GermanyHospital Pharmacy, Heidelberg University Hospital, 69120 Heidelberg, GermanyMedical Microbiology and Hygiene, Department of Infectious Diseases, Heidelberg University Hospital, 69120 Heidelberg, GermanyMedical Microbiology and Hygiene, Department of Infectious Diseases, Heidelberg University Hospital, 69120 Heidelberg, GermanyHospital Pharmacy, Heidelberg University Hospital, 69120 Heidelberg, GermanyMedical Microbiology and Hygiene, Department of Infectious Diseases, Heidelberg University Hospital, 69120 Heidelberg, GermanyMedical Microbiology and Hygiene, Department of Infectious Diseases, Heidelberg University Hospital, 69120 Heidelberg, GermanyThe 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.https://www.mdpi.com/2079-6382/11/5/581cefiderocolbeta-lactam antibioticendothelial barriervascular leakage |
| spellingShingle | Dagmar Hildebrand Jana Böhringer Eva Körner Ute Chiriac Sandra Förmer Aline Sähr Torsten Hoppe-Tichy Klaus Heeg Dennis Nurjadi Cefiderocol Protects against Cytokine- and Endotoxin-Induced Disruption of Vascular Endothelial Cell Integrity in an In Vitro Experimental Model Antibiotics cefiderocol beta-lactam antibiotic endothelial barrier vascular leakage |
| 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 | cefiderocol beta-lactam antibiotic endothelial barrier vascular leakage |
| url | https://www.mdpi.com/2079-6382/11/5/581 |
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