Crohn's Disease Patients with Depression Exhibit Alterations in Monocyte/Macrophage Phenotype and Increased Proinflammatory Cytokine Production
Crohn's Disease Patients with Depression Exhibit Alterations in Monocyte/Macrophage Phenotype and Increased Proinflammatory Cytokine Production
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患有抑郁症的克罗恩病患者表现出单核细胞/巨噬细胞表型的改变和促炎细胞因子产生的增加
DOI：
10.1159/000501122
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发表时间：
2020-05-01
影响因子：
2.3
通讯作者：
Zhang, Yan
中科院分区：
文献类型：
--
作者：
Tang, Yu;Zhao, Li;Zhang, Yan
背景：克罗恩病（CD）与抑郁症密切相关，但这种关系的机制尚未完全了解。近年来，神经免疫学研究表明，促炎单核/巨噬细胞在抑郁症的发病机制中起着关键作用。本研究探讨了CD患者的单核细胞/巨噬细胞表型和血浆细胞因子水平。研究方法：根据医院焦虑抑郁量表（HADS-D）将符合条件的CD患者分为非抑郁组和抑郁组。比较两组之间的Harvey-Bradshaw指数（HBI）、克罗恩病简易内镜评分（SES-CD）和总体组织学疾病活动评分（GHAS）。免疫组化检测结肠黏膜中CD 68、诱导型一氧化氮合酶（iNOS）和CD 163的表达。采用酶联免疫吸附试验检测M1巨噬细胞分泌的细胞因子（肿瘤坏死因子[TNF]-α、-白细胞介素6 [IL-6]、IL-1 β）和M2细胞因子（转化生长因子[TGF]-β 1、IL-10、C-C基序趋化因子配体22 [CCL 22]）的血浆水平。采用流式细胞术测定外周血单核细胞亚群。结果：抑郁组（n = 91）的HBI、-SES-CD、GHAS均高于非抑郁组（n = 42）。中间（CD 14 ++ CD 16+）和非经典单核细胞（CD 14 + CD 16 ++）百分比，代表M1巨噬细胞的iNOS+细胞的积分光密度（IOD）和TNF-α，IL-6，IL-1 β的血浆水平增加，而经典单核细胞与非抑郁CD患者相比，抑郁CD患者的（CD 14 ++ CD 16-）百分比、代表M2巨噬细胞的CD 163+细胞的IOD和IL-10血浆水平降低。血浆TNF-α、IL-6、IL-1 β水平与HADS-D评分相关。结论：单核细胞亚群向中间和非经典表型和巨噬细胞向M1表型极化与促炎细胞因子释放增加的不平衡更可能被发现在CD患者抑郁症状。
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]-alpha, -interleukin 6 [IL-6], IL-1 beta) and M2 cytokines (transforming growth factor [TGF]-beta 1, 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-alpha, IL-6, IL-1 beta 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-alpha, IL-6, IL-1 beta 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.