Monocytes from infliximab-resistant patients with Crohn's disease exhibit a disordered cytokine profile.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
22 07 2020
22 07 2020
Historique:
received:
11
04
2020
accepted:
03
07
2020
entrez:
24
7
2020
pubmed:
24
7
2020
medline:
2
12
2020
Statut:
epublish
Résumé
Crohn's disease (CD) is a chronic inflammatory disorder characterized by immune response dysregulation. Tumor necrosis factor-α (TNFα) is a key cytokine in the pathogenesis of CD, as indicated by the efficacy of anti-TNF-α therapy with infliximab (IFX). However, approximately 30-40% of CD patients fail to respond to IFX with still unclear underlying mechanisms. This study compares the inflammatory phenotype of monocytes from CD patients, who respond or non-respond to IFX. Under basal conditions, the mRNA for the cytokines TNFα, IL-23, IL-1β and the chemokines CXCL8/IL-8, CCL5/RANTES and CCL2/MCP-1 was up-regulated in monocytes from non-responders than responders. The expression of the same cytokines and CCL2/MCP-1 was higher in non-responders also upon LPS treatment. Moreover, higher secretion of TNFα, IL-1β, IFNγ and IL-2 proteins occurred in the supernatants of LPS-treated non-responders cells. Resistance to IFX in CD may result from a transcriptional dysregulation of circulating monocytes, leading to hyperactivation of pro-inflammatory pathways. Monocytes' cytokine profile may thus represent a predictive marker of response to IFX. Monocytes were isolated from blood samples of 19 CD patients (11 responders, 8 non-responders) and incubated with or without LPS. Cytokine profiles were assessed by RT-qPCR and, in the supernatants, by ELISA assay.
Identifiants
pubmed: 32699266
doi: 10.1038/s41598-020-68993-1
pii: 10.1038/s41598-020-68993-1
pmc: PMC7376177
doi:
Substances chimiques
Cytokines
0
Infliximab
B72HH48FLU
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
12238Références
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