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

• Published in: Scientific reports Vol. 10; no. 1; p. 12238
• Main Authors: Gaiani, Federica, Rotoli, Bianca Maria, Ferrari, Francesca, Barilli, Amelia, Visigalli, Rossana, Carra, Maria Clotilde, de’Angelis, Gian Luigi, de’Angelis, Nicola, Dall’Asta, Valeria
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22.07.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 631/250; 631/80; 692/4020; Chemokines; Crohn's disease; Cytokines; Enzyme-linked immunosorbent assay; Humanities and Social Sciences; IL-1β; Immune response; Immunotherapy; Inflammatory bowel diseases; Infliximab; Interleukin 2; Interleukin 23; Interleukin 8; Lipopolysaccharides; Monoclonal antibodies; Monocyte chemoattractant protein 1; Monocytes; multidisciplinary; Phenotypes; RANTES; Science; Science (multidisciplinary); TNF inhibitors; Transcription; Tumor necrosis factor-TNF; Tumor necrosis factor-α; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-68993-1

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.