Yu Tang1, Li Zhao1, Na Lei1, Pingrun Chen1, Yan Zhang2. 1. Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, China. 2. Department of Gastroenterology, West China Hospital of Sichuan University, Chengdu, China, huaxizyan@163.com.
Abstract
BACKGROUND: Crohn's disease (CD) is strongly associated with depression, but the mechanisms underlying this relationship are not fully understood. Recently, neuroimmunological studies have demonstrated that proinflammatory monocytes/macrophages play a key role in the pathogenesis of depression. The present study investigates monocyte/macrophage phenotypes and plasma cytokine levels in CD. METHODS: Eligible CD patients were divided into nondepressed and depressed groups according to Hospital Anxiety and Depression Scale for depression (HADS-D). The Harvey-Bradshaw index (HBI), the Simple Endoscopic Score for Crohn's disease (SES-CD), and the Global Histological Disease Activity Score (GHAS) were compared between the 2 groups. Immunohistochemistry was performed to quantify the expression of CD68, inducible nitic oxide synthase (iNOS), and CD163 in colon mucosa. Enzyme-linked Immunosorbent Assay was used to detect plasma levels of M1 macrophage-secreted cytokines (tumor necrosis factor [TNF]-α, -interleukin 6 [IL-6], IL-1β) and M2 cytokines (transforming growth factor [TGF]-β1, IL-10, C-C motif chemokine ligand 22, [CCL22]). Flow cytometry was utilized to determine peripheral blood monocyte subsets. RESULTS: Depressed CD patients (n = 91) presented higher HBI, -SES-CD, GHAS than the nondepressed patients (n = 42). Intermediate (CD14++CD16+) and nonclassical monocytes (CD14+CD16++) percentages, integrated optical density (IOD) of iNOS+ cells representing M1 macrophages, and plasma levels of TNF-α, IL-6, IL-1β were increased while -classical monocyte (CD14++CD16-) percentage, IOD of CD163+ cells representing M2 macrophages, and IL-10 plasma levels were decreased in depressed versus nondepressed CD patients. Plasma levels of TNF-α, IL-6, IL-1β correlated with HADS-D scores. CONCLUSION: Monocytes subpopulation disequilibrium toward intermediate and nonclassic phenotypes and macrophage polarization toward M1 phenotype with increased proinflammatory cytokine release are more likely to be found in CD patients with depressive symptoms.
BACKGROUND:Crohn's disease (CD) is strongly associated with depression, but the mechanisms underlying this relationship are not fully understood. Recently, neuroimmunological studies have demonstrated that proinflammatory monocytes/macrophages play a key role in the pathogenesis of depression. The present study investigates monocyte/macrophage phenotypes and plasma cytokine levels in CD. METHODS: Eligible CDpatients were divided into nondepressed and depressed groups according to Hospital Anxiety and Depression Scale for depression (HADS-D). The Harvey-Bradshaw index (HBI), the Simple Endoscopic Score for Crohn's disease (SES-CD), and the Global Histological Disease Activity Score (GHAS) were compared between the 2 groups. Immunohistochemistry was performed to quantify the expression of CD68, inducible nitic oxide synthase (iNOS), and CD163 in colon mucosa. Enzyme-linked Immunosorbent Assay was used to detect plasma levels of M1 macrophage-secreted cytokines (tumor necrosis factor [TNF]-α, -interleukin 6 [IL-6], IL-1β) and M2 cytokines (transforming growth factor [TGF]-β1, IL-10, C-C motif chemokine ligand 22, [CCL22]). Flow cytometry was utilized to determine peripheral blood monocyte subsets. RESULTS:Depressed CDpatients (n = 91) presented higher HBI, -SES-CD, GHAS than the nondepressed patients (n = 42). Intermediate (CD14++CD16+) and nonclassical monocytes (CD14+CD16++) percentages, integrated optical density (IOD) of iNOS+ cells representing M1 macrophages, and plasma levels of TNF-α, IL-6, IL-1β were increased while -classical monocyte (CD14++CD16-) percentage, IOD of CD163+ cells representing M2 macrophages, and IL-10 plasma levels were decreased in depressed versus nondepressed CD patients. Plasma levels of TNF-α, IL-6, IL-1β correlated with HADS-D scores. CONCLUSION: Monocytes subpopulation disequilibrium toward intermediate and nonclassic phenotypes and macrophage polarization toward M1 phenotype with increased proinflammatory cytokine release are more likely to be found in CDpatients with depressive symptoms.
Authors: Alexander R Siebenhüner; Jean-Benoît Rossel; Philipp Schreiner; Matthias Butter; Thomas Greuter; Niklas Krupka; Sebastian B U Jordi; Luc Biedermann; Gerhard Rogler; Benjamin Misselwitz; Roland von Känel Journal: Therap Adv Gastroenterol Date: 2021-08-31 Impact factor: 4.409