Crohn's disease (CD) is a chronic inflammatory disorder characterized by immune response dysregulation. Tumor necrosis factor-alpha (TNF alpha) is a key cytokine in the pathogenesis of CD, as indicated by the efficacy of anti-TNF-alpha 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 TNF alpha, IL-23, IL-1 beta 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 TNF alpha, IL-1 beta, IFN gamma 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.

Monocytes from infliximab-resistant patients with Crohn's disease exhibit a disordered cytokine profile

Carra M;De' Angelis N;
2020

Abstract

Crohn's disease (CD) is a chronic inflammatory disorder characterized by immune response dysregulation. Tumor necrosis factor-alpha (TNF alpha) is a key cytokine in the pathogenesis of CD, as indicated by the efficacy of anti-TNF-alpha 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 TNF alpha, IL-23, IL-1 beta 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 TNF alpha, IL-1 beta, IFN gamma 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.
2020
Gaiani, F; Rotoli, Bm; Ferrari, F; Barilli, A; Visigalli, R; Carra, M; De'Angelis, Gl; De' Angelis, N; Dall'Asta, V.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2533172
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