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白细胞介素-19的表达与尿毒症患者的辅助性T细胞2细胞因子相关。

Expression of IL-19 correlates with Th2 cytokines in uraemic patients.

作者信息

Hsing Chung-Hsi, Hsu Chuan-Chih, Chen Wei-Yu, Chang Lih-Yun, Hwang Jyh-Chang, Chang Ming-Shi

机构信息

Institute of Biopharmaceutical Sciences, National Cheng Kung University, Tainan, Taiwan.

出版信息

Nephrol Dial Transplant. 2007 Aug;22(8):2230-8. doi: 10.1093/ndt/gfm179. Epub 2007 Apr 20.

Abstract

BACKGROUND

Patients with end-stage renal disease are thought to be in a chronic state of inflammation. They also have an impaired immune response with a dysregulated Th1/Th2 cytokine network. Interleukin (IL)-19, which belongs to the IL-10 family, is a newly discovered proinflammatory cytokine. IL-19 alters the balance of Th1/Th2 cells in favour of Th2. The aims of the present study were to assess the changes in serum levels of IL-19 and their correlation with Th2 cytokine production in uraemic patients.

METHODS

Seventy-three uraemic patients with haemodialysis were evaluated; 33 healthy volunteers served as controls. Serum levels of IL-19, -4, -5, -6, -10, -13 and tumour necrosis factor (TNF)-alpha were analysed using ELISA. Monocytes and T cells isolated from the patients and healthy volunteers were cultured in vitro, and cytokine production was determined.

RESULTS

IL-19 expression in the patients; but not in healthy controls, correlated positively with both the proinflammatory cytokines (IL-6 and TNF-alpha) and the Th2 cytokines (IL-4, IL-5, IL-6, IL-10 and IL-13). Cultured monocytes from patients with high IL-19 serum levels produced more IL-19 in vitro. Additionally, uraemic serum or oxidized low-density lipoproteins up-regulated the IL-19 transcripts expression in resting monocytes. Compared with T cells from healthy controls, uraemic T cells expressed more endogenous Th2 cytokine transcripts and further responded to IL-19 stimulation in Th2 cytokine production in vitro.

CONCLUSIONS

IL-19 expression in uraemic patients correlated with Th2 immune responses which might be involved in the cytokine dysregulation in uraemia.

摘要

背景

终末期肾病患者被认为处于慢性炎症状态。他们还存在免疫反应受损,Th1/Th2细胞因子网络失调。白细胞介素(IL)-19属于IL-10家族,是一种新发现的促炎细胞因子。IL-19改变Th1/Th2细胞平衡,使其向Th2倾斜。本研究的目的是评估尿毒症患者血清IL-19水平的变化及其与Th2细胞因子产生的相关性。

方法

对73例接受血液透析的尿毒症患者进行评估;33名健康志愿者作为对照。采用酶联免疫吸附测定法(ELISA)分析血清中IL-19、-4、-5、-6、-10、-13及肿瘤坏死因子(TNF)-α的水平。从患者和健康志愿者中分离出单核细胞和T细胞进行体外培养,并测定细胞因子的产生情况。

结果

患者体内IL-19的表达与促炎细胞因子(IL-6和TNF-α)及Th2细胞因子(IL-4、IL-5、IL-6、IL-10和IL-13)均呈正相关,而健康对照者体内则无此相关性。IL-19血清水平高的患者的培养单核细胞在体外产生更多IL-19。此外,尿毒症血清或氧化型低密度脂蛋白上调静息单核细胞中IL-19转录本的表达。与健康尿毒症T细胞相比,尿毒症T细胞表达更多内源性Th2细胞因子转录本,并且在体外对IL-19刺激产生Th2细胞因子的反应更强。

结论

尿毒症患者IL-19的表达与Th2免疫反应相关,这可能参与了尿毒症患者的细胞因子失调。

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