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Pons S, Arrii E, Arnaud M, et al. Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation. Immun Inflamm Dis. 2021;9(4):1656-1669doi: 10.1002/iid3.518.
Pons, S., Arrii, E., Arnaud, M., Loiselle, M., Ferry, J., Nouacer, M., Lion, J., Cohen, S., Mooney, N., & Zafrani, L. (2021). Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation. Immunity, inflammation and disease, 9(4), 1656-1669. https://doi.org/10.1002/iid3.518
Pons, Stéphanie, et al. "Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation." Immunity, inflammation and disease vol. 9,4 (2021): 1656-1669. doi: https://doi.org/10.1002/iid3.518
Pons S, Arrii E, Arnaud M, Loiselle M, Ferry J, Nouacer M, Lion J, Cohen S, Mooney N, Zafrani L. Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation. Immun Inflamm Dis. 2021 Dec;9(4):1656-1669. doi: 10.1002/iid3.518. Epub 2021 Oct 12. PMID: 34636179; PMCID: PMC8589380.
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Immun Inflamm Dis. 2021 Dec;9(4):1656-1669. doi: 10.1002/iid3.518. Epub 2021 Oct 12.

Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation.

Immunity, inflammation and disease

Stéphanie Pons, Eden Arrii, Marine Arnaud, Maud Loiselle, Juliette Ferry, Manel Nouacer, Julien Lion, Shannon Cohen, Nuala Mooney, Lara Zafrani

Affiliations

  1. Human Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976, Université de Paris, Paris, France.
  2. Department of Anesthesiology and Critical Care, Pitié-Salpêtrière Hospital, GRC 29, AP-HP, DMU DREAM, Sorbonne University, Paris, France.
  3. Medical Intensive Care Unit, AP-HP, Saint-Louis Teaching Hospital, Paris, France.

PMID: 34636179 PMCID: PMC8589380 DOI: 10.1002/iid3.518

Abstract

OBJECTIVES: Sepsis is defined as the host's inflammatory response to a life-threatening infection. The endothelium is implicated in immunoregulation during sepsis. Macrolides have been proposed to display immunomodulatory properties. The goal of this study was to analyze whether macrolides can exert immunomodulation of endothelial cells (ECs) in an experimental model of sepsis.

METHODS: Human ECs were stimulated by proinflammatory cytokines and lipopolysaccharide before exposure to macrolides. ECs phenotypes were analyzed by flow cytometry. Cocultures of ECs and peripheral blood mononuclear cells (PBMCs) were performed to study the ECs ability to alter T-cell viability and differentiation in the presence of macrolides. Soluble factor production was assessed.

RESULTS: ECs act as non-professional antigen presenting cells and expressed human leukocyte antigen (HLA) antigens, the adhesion molecules CD54, CD106, and the coinhibitory molecule CD274 after septic stimulation. Incubation with macrolides induced a significant decrease of HLA class I and HLA class II HLA-DR on septic-stimulated ECs, but did not alter either CD54, CD106, nor CD274 expression. Interleukin-6 (IL-6) and IL-8 production by stimulated ECs were unaltered by incubation with macrolides, whereas Clarithromycin exposure significantly decreased IL-6 gene expression. In cocultures of septic ECs with PBMCs, neither the proportion of CD4 

CONCLUSION: This study reports phenotypic and gene expression changes in septic-stimulated ECs exposed to macrolides, without resulting in altered immunogenicity of ECs in co-cultures with PBMCs. In vivo studies may help to further understand the impact of macrolide therapy on ECs immune homeostasis during sepsis.

© 2021 John Wiley & Sons Ltd.

Keywords: antibiotics; endothelium; immunoregulation; inflammation; septic shock

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