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慢性或复发性Vogt-小柳-原田病中白细胞介素21的上调及白细胞介素17产生的促进

Upregulation of interleukin 21 and promotion of interleukin 17 production in chronic or recurrent Vogt-Koyanagi-Harada disease.

作者信息

Li Fuzhen, Yang Peizeng, Liu Xiaoli, Wang Chaokui, Hou Shengping, Kijlstra Aize

机构信息

Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China.

出版信息

Arch Ophthalmol. 2010 Nov;128(11):1449-54. doi: 10.1001/archophthalmol.2010.265.

Abstract

OBJECTIVES

To analyze the expression and potential role of interleukin (IL) 21 in the pathogenesis of Vogt-Koyanagi-Harada (VKH) disease.

METHODS

Blood samples were obtained from patients with VKH disease and from healthy control subjects. Serum IL-21 level and IL-21 messenger RNA (mRNA) expression by peripheral blood mononuclear cells (PBMCs) were determined by enzyme-linked immunosorbent assay and by reverse transcriptase-polymerase chain reaction, respectively. Interleukin 17 and interferon γ levels in the supernatants of PBMCs and CD4(+) T cells cultured with anti-CD3 and anti-CD28 antibodies in the presence or absence of recombinant IL-21 were detected by enzyme-linked immunosorbent assay.

RESULTS

The results showed a significantly increased serum IL-21 level, as well as higher IL-21 mRNA expression by PBMCs, in patients having chronic or recurrent active VKH disease compared with patients having inactive VKH disease and with controls. In vitro experiments showed that recombinant IL-21 significantly increased IL-17 production by PBMCs and by CD4(+) T cells from patients and from controls. However, recombinant IL-21 did not affect interferon γ expression by PBMCs or by CD4(+) T cells.

CONCLUSION

Interleukin 21 may be involved in the pathogenesis of chronic or recurrent VKH disease, possibly by promoting IL-17 secretion.

CLINICAL RELEVANCE

Findings from the present study suggest that IL-21 may be a potential target in the development of therapy for VKH disease.

摘要

目的

分析白细胞介素(IL)-21在Vogt-小柳-原田(VKH)病发病机制中的表达及潜在作用。

方法

采集VKH病患者和健康对照者的血样。分别采用酶联免疫吸附测定法和逆转录-聚合酶链反应法测定血清IL-21水平及外周血单个核细胞(PBMC)中IL-21信使核糖核酸(mRNA)的表达。采用酶联免疫吸附测定法检测在有或无重组IL-21存在的情况下,用抗CD3和抗CD28抗体培养的PBMC和CD4(+)T细胞上清液中的白细胞介素17和干扰素γ水平。

结果

结果显示,与非活动性VKH病患者及对照组相比,慢性或复发性活动性VKH病患者的血清IL-21水平显著升高,PBMC中IL-21 mRNA的表达也更高。体外实验表明,重组IL-21可显著增加患者及对照者PBMC和CD4(+)T细胞产生的IL-17。然而,重组IL-21并不影响PBMC或CD4(+)T细胞的干扰素γ表达。

结论

白细胞介素21可能参与慢性或复发性VKH病的发病机制,可能是通过促进IL-17的分泌。

临床意义

本研究结果表明,IL-21可能是VKH病治疗开发中的一个潜在靶点。

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