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Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile
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 patie...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376177/ https://www.ncbi.nlm.nih.gov/pubmed/32699266 http://dx.doi.org/10.1038/s41598-020-68993-1 |
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author | Gaiani, Federica Rotoli, Bianca Maria Ferrari, Francesca Barilli, Amelia Visigalli, Rossana Carra, Maria Clotilde de’Angelis, Gian Luigi de’Angelis, Nicola Dall’Asta, Valeria |
author_facet | Gaiani, Federica Rotoli, Bianca Maria Ferrari, Francesca Barilli, Amelia Visigalli, Rossana Carra, Maria Clotilde de’Angelis, Gian Luigi de’Angelis, Nicola Dall’Asta, Valeria |
author_sort | Gaiani, Federica |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-7376177 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-73761772020-07-24 Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile Gaiani, Federica Rotoli, Bianca Maria Ferrari, Francesca Barilli, Amelia Visigalli, Rossana Carra, Maria Clotilde de’Angelis, Gian Luigi de’Angelis, Nicola Dall’Asta, Valeria Sci Rep Article 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. Nature Publishing Group UK 2020-07-22 /pmc/articles/PMC7376177/ /pubmed/32699266 http://dx.doi.org/10.1038/s41598-020-68993-1 Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Gaiani, Federica Rotoli, Bianca Maria Ferrari, Francesca Barilli, Amelia Visigalli, Rossana Carra, Maria Clotilde de’Angelis, Gian Luigi de’Angelis, Nicola Dall’Asta, Valeria Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile |
title | Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile |
title_full | Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile |
title_fullStr | Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile |
title_full_unstemmed | Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile |
title_short | Monocytes from infliximab-resistant patients with Crohn’s disease exhibit a disordered cytokine profile |
title_sort | monocytes from infliximab-resistant patients with crohn’s disease exhibit a disordered cytokine profile |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376177/ https://www.ncbi.nlm.nih.gov/pubmed/32699266 http://dx.doi.org/10.1038/s41598-020-68993-1 |
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