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与代谢健康的肥胖个体相比,肥胖且患有2型糖尿病的个体存在额外的免疫功能障碍。

Individuals with obesity and type 2 diabetes have additional immune dysfunction compared with obese individuals who are metabolically healthy.

作者信息

Richard Caroline, Wadowski Michael, Goruk Susan, Cameron Lisa, Sharma Arya M, Field Catherine J

机构信息

Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, Alberta, Canada.

Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.

出版信息

BMJ Open Diabetes Res Care. 2017 May 8;5(1):e000379. doi: 10.1136/bmjdrc-2016-000379. eCollection 2017.

Abstract

OBJECTIVE

The objective of the current study was to compare the responses to different ex vivo immunogenic challenges between immune cells derived from metabolically healthy subjects with obesity and subjects with obesity and type 2 diabetes.

RESEARCH DESIGN AND METHODS

We recruited 10 metabolically healthy subjects with obesity (Edmonton Obesity Staging System (EOSS) stage 0) and 9 subjects with obesity and type 2 diabetes (EOSS stage 2) aged between 21 years and 70 years and matched for body mass index. Peripheral blood mononuclear cells (PBMCs) were isolated and immune cell phenotypes and ex vivo cytokine production after phytohaemagglutinin (PHA, a T cell mitogen) stimulation were determined. Neutrophil oxidative burst activity was assessed in whole blood.

RESULTS

PBMCs from subjects with stage 2 obesity produced significantly less interleukin (IL)-2, IL-6 and tumour necrosis factor α after PHA stimulation than PBMCs from subjects with stage 0 obesity (all, p<0.05). Subjects with stage 2 obesity also had higher proportions of cytotoxic T cells, activated helper T cells (CD4+CD278+) and inflammatory monocytes (CD14+CRTh2+, all p<0.05). Poststimulation, neutrophils from subjects with stage 2 obesity produced significantly more free radicals, were larger and more granular and had a lower stimulation index (all p<0.05).

CONCLUSIONS

Our results suggest that compared with obese individuals metabolically healthy individuals with obesity and type 2 diabetes have an impaired neutrophil function and T cell response on challenge despite having a T cell population expressing more activation markers which may be partly responsible for the increased prevalence of infection reported in this population.

摘要

目的

本研究的目的是比较肥胖的代谢健康受试者与肥胖合并2型糖尿病受试者的免疫细胞对不同体外免疫原刺激的反应。

研究设计与方法

我们招募了10名年龄在21岁至70岁之间、身体质量指数相匹配的肥胖代谢健康受试者(埃德蒙顿肥胖分期系统(EOSS)0期)和9名肥胖合并2型糖尿病受试者(EOSS 2期)。分离外周血单个核细胞(PBMC),并测定植物血凝素(PHA,一种T细胞有丝分裂原)刺激后免疫细胞表型和体外细胞因子产生情况。在全血中评估中性粒细胞氧化爆发活性。

结果

与0期肥胖受试者的PBMC相比,2期肥胖受试者的PBMC在PHA刺激后产生的白细胞介素(IL)-2、IL-6和肿瘤坏死因子α显著减少(均p<0.05)。2期肥胖受试者的细胞毒性T细胞、活化辅助性T细胞(CD4+CD278+)和炎性单核细胞(CD14+CRTh2+)比例也更高(均p<0.05)。刺激后,2期肥胖受试者的中性粒细胞产生的自由基显著增多,体积更大、颗粒更多,刺激指数更低(均p<0.05)。

结论

我们的结果表明,与肥胖个体相比,肥胖合并2型糖尿病的代谢健康个体在受到刺激时中性粒细胞功能和T细胞反应受损,尽管其T细胞群体表达更多活化标志物,这可能是该人群感染患病率增加的部分原因。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/28cd/5530252/e9f88f09f186/bmjdrc-2016-000379f01.jpg

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