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低干扰素-γ和白细胞介素-10水平对2型糖尿病患者中PHA诱导的外周血单个核细胞产生肿瘤坏死因子-α和白细胞介素-6的影响

Impact of Low Interferon-γ and IL-10 Levels on TNF-α and IL-6 Production by PHA-Induced PBMCs in Type 2 Diabetes Mellitus.

作者信息

Kartika Rona, Purnamasari Dyah, Pradipta Saraswati, Larasati Rahma A, Wibowo Heri

机构信息

Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.

Division of Metabolic Endocrinology and Diabetes, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.

出版信息

J Inflamm Res. 2020 Apr 22;13:187-193. doi: 10.2147/JIR.S245064. eCollection 2020.

DOI:10.2147/JIR.S245064
PMID:32425577
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7190380/
Abstract

PURPOSE

In this study, we analyzed the production of interferon γ (IFN-γ) and interleukin 10 (IL-10) by peripheral blood mononuclear cells (PBMCs) in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the capacity of monocytes to produce tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) following IFN-γ stimulation and the associated role of IL-10 in TNF-α and IL-6 production.

PATIENTS AND METHODS

In vitro experiments were conducted on PBMCs obtained from 19 patients with T2DM and 17 healthy participants. PBMCs were isolated from venous blood by density gradient centrifugation, followed by 3-day phytohemagglutinin induction. In vitro production of TNF-α, IL-6, IFN-γ, and IL-10 was measured using the multiplex immunoassay. Statistical analysis was performed using IBM SPSS 23 version.

RESULTS

IFN-γ concentration in the T2DM group was significantly lower than that in control group (T2DM 7,700.86 ± 3,037.77 vs control 10,672.69 ± 5,625.50 pg/mL; = 0.048). However, TNF-α, IL-6, and IL-10 levels showed no significant difference between the two groups. The TNF-α/IFN-γ and IL-6/IFN-γ ratios were significantly higher in T2DM than in the control group ( = 0.026 and = 0.048, respectively). In T2DM, the high TNF-α/IFN-γ ratio was consistent, with the low baseline IL-10 level ( = 0.022).

CONCLUSION

In T2DM, T-cell response is impaired with significantly reduced IFN-γ production, and simultaneously, circulatory monocytes show enhanced cellular responsiveness to inflammatory stimuli. The low baseline IL-10 level likely contributes to such an immune response.

摘要

目的

在本研究中,我们分析了2型糖尿病(T2DM)患者外周血单个核细胞(PBMC)中干扰素γ(IFN-γ)和白细胞介素10(IL-10)的产生情况。我们旨在研究单核细胞在IFN-γ刺激后产生肿瘤坏死因子-α(TNF-α)和白细胞介素6(IL-6)的能力以及IL-10在TNF-α和IL-6产生中的相关作用。

患者与方法

对19例T2DM患者和17名健康参与者的PBMC进行体外实验。通过密度梯度离心从静脉血中分离PBMC,随后进行3天的植物血凝素诱导。使用多重免疫测定法测量TNF-α、IL-6、IFN-γ和IL-10的体外产生情况。使用IBM SPSS 23版本进行统计分析。

结果

T2DM组中的IFN-γ浓度显著低于对照组(T2DM组为7,700.86±3,037.77 vs对照组为10,672.69±5,625.50 pg/mL;P = 0.048)。然而,两组之间的TNF-α、IL-6和IL-10水平无显著差异。T2DM组中的TNF-α/IFN-γ和IL-6/IFN-γ比值显著高于对照组(分别为P = 0.026和P = 0.048)。在T2DM中,高TNF-α/IFN-γ比值与低基线IL-10水平一致(P = 0.022)。

结论

在T2DM中,T细胞反应受损,IFN-γ产生显著减少,同时,循环单核细胞显示出对炎症刺激的细胞反应性增强。低基线IL-10水平可能导致了这种免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/7190380/fa097d6fdf61/JIR-13-187-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/7190380/ac3a5adfae3a/JIR-13-187-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/7190380/fa097d6fdf61/JIR-13-187-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/7190380/ac3a5adfae3a/JIR-13-187-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/330f/7190380/fa097d6fdf61/JIR-13-187-g0002.jpg

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