Differential response induced by LPS and MPLA in immunocompetent and septic individuals
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Veröffentlicht in: | Clinical immunology (Orlando, Fla.). - 1999. - 226(2021) vom: 30. Mai, Seite 108714 |
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1. Verfasser: | |
Weitere Verfasser: | , , , , , , , |
Format: | Online-Aufsatz |
Sprache: | English |
Veröffentlicht: |
2021
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Zugriff auf das übergeordnete Werk: | Clinical immunology (Orlando, Fla.) |
Schlagworte: | Clinical Trial Journal Article Randomized Controlled Trial Immune functional assay LPS MPLA Sepsis Septic patients Stratification Cytokines mehr... |
Zusammenfassung: | Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved. Lipopolysaccharide (LPS) and monophosphoryl lipid A (MPLA) induce, overall, similar transcriptional profiles in healthy individuals, although LPS has been shown to more potently induce pro-inflammatory cytokines. We explore herein whether MPLA could be considered as a synthetic replacement of LPS in immune functional assays to study anergy of immune cells in septic patients. Ex vivo whole blood stimulation with MPLA revealed a lower induction of the TNFα secreted protein in 20 septic patients (SP) compared to 10 healthy volunteers (HV), in agreement with monocyte anergy. Principal component analysis of the 93-gene molecular response to MPLA and LPS stimulation found that the main variability was driven by stimulation in HV and by pathophysiology in SP. MPLA was a stronger inducer of the HLA family genes than LPS in both populations, arguing for divergent signalling pathways downstream of TLR-4. In addition, MPLA appeared to present a more informative stratification potential within the septic population |
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Beschreibung: | Date Completed 24.06.2021 Date Revised 24.06.2021 published: Print-Electronic Citation Status MEDLINE |
ISSN: | 1521-7035 |
DOI: | 10.1016/j.clim.2021.108714 |