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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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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\u2010cell viability and differentiation in the presence of macrolides. Soluble factor production was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ECs act as non\u2010professional 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\u2010DR on septic\u2010stimulated ECs, but did not alter either CD54, CD106, nor CD274 expression. Interleukin\u20106 (IL\u20106) and IL\u20108 production by stimulated ECs were unaltered by incubation with macrolides, whereas Clarithromycin exposure significantly decreased IL\u20106 gene expression. In cocultures of septic ECs with PBMCs, neither the proportion of CD4\u2009<jats:sup>+\u2009<\/jats:sup>, CD8\u2009<jats:sup>+\u2009<\/jats:sup>T nor their viability was altered by macrolides. T\u2010helper lymphocyte subsets Th1, Th17, and Treg polarization by stimulated ECs were unaltered by macrolides.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study reports phenotypic and gene expression changes in septic\u2010stimulated ECs exposed to macrolides, without resulting in altered immunogenicity of ECs in co\u2010cultures with PBMCs. In vivo studies may help to further understand the impact of macrolide therapy on ECs immune homeostasis during sepsis.<\/jats:p><\/jats:sec>","DOI":"10.1002\/iid3.518","type":"journal-article","created":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T15:15:59Z","timestamp":1634310959000},"page":"1656-1669","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Immunomodulation of endothelial cells induced by macrolide therapy in a model of septic stimulation"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7372-3563","authenticated-orcid":false,"given":"St\u00e9phanie","family":"Pons","sequence":"first","affiliation":[{"name":"Human Immunology, Pathophysiology, Immunotherapy (HIPI), INSERM U976 Universit\u00e9 de Paris  Paris France"},{"name":"Department of Anesthesiology and Critical Care, Piti\u00e9\u2010Salp\u00eatri\u00e8re Hospital, GRC 29, AP\u2010HP, DMU DREAM Sorbonne 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