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双重滤过血浆置换成功治疗大疱性类天疱疮患者:对患者外周血单个核细胞中几种趋化因子和细胞因子基因转录本的体内影响

Successful treatment by double-filtration plasmapheresis of a patient with bullous pemphigoid: effects in vivo on transcripts of several genes for chemokines and cytokines in peripheral blood mononuclear cells.

作者信息

Hatano Y, Katagiri K, Arakawa S, Umeki T, Takayasu S, Fujiwara S

机构信息

Department of Dermatology, Oita Medical University, 1-1 Idaigaoka, Hasama-machi, Oita-gun, Oita 879-5593, Japan.

出版信息

Br J Dermatol. 2003 Mar;148(3):573-9. doi: 10.1046/j.1365-2133.2003.05233.x.

DOI:10.1046/j.1365-2133.2003.05233.x
PMID:12653753
Abstract

The involvement of various cytokines and chemokines has been reported in the pathogenesis of bullous pemphigoid (BP). Double-filtration plasmapheresis (DFPP) is an effective treatment for BP but the mechanism of action remains unclear. Using semiquantitative reverse transcription-polymerase chain reaction, we examined levels of transcripts for various cytokines and chemokines in freshly isolated peripheral blood mononuclear cells in a patient with BP before and after DFPP treatment. DFPP was performed four times. Relative levels of transcripts for interleukin (IL)-8, macrophage inflammatory protein (MIP)-1alpha and IL-5, and the ratio of relative levels of transcripts for IL-4 and interferon (IFN)-gamma, were higher, before treatment, than in healthy controls, and decreased when the extent of the lesions was reduced. Relative levels of transcripts for tumour necrosis factor (TNF)-alpha and IL-4 also decreased with regression of lesions, although they were similar to or lower than the corresponding levels in healthy individuals. When eruptions recurred, relative levels of transcripts for IL-8, MIP-1alpha, RANTES (regulated upon activation normal T cell expressed and secreted), IL-2, IFN-gamma and TNF-alpha were very much higher than those prior to the recurrence, while relative levels of mRNAs for IL-4 and IL-5 did not increase. Relative levels of transcripts for IL-8, MIP-1alpha, TNF-alpha and IL-2 were lower at the end of each individual DFPP and after the four treatments than at the beginning of treatment. Our observations suggest that cytokines and chemokines produced in mononuclear cells play important roles in the pathogenesis of BP and that regulation of their expression might be involved in the therapeutic effects of DFPP in BP.

摘要

已有报道称多种细胞因子和趋化因子参与大疱性类天疱疮(BP)的发病机制。双重滤过血浆置换(DFPP)是治疗BP的一种有效方法,但其作用机制尚不清楚。我们采用半定量逆转录-聚合酶链反应,检测了1例BP患者在DFPP治疗前后新鲜分离的外周血单个核细胞中多种细胞因子和趋化因子的转录水平。进行了4次DFPP。治疗前,白细胞介素(IL)-8、巨噬细胞炎性蛋白(MIP)-1α和IL-5的转录相对水平以及IL-4与干扰素(IFN)-γ转录相对水平的比值高于健康对照,且随着皮损范围缩小而降低。肿瘤坏死因子(TNF)-α和IL-4的转录相对水平也随着皮损消退而降低,尽管它们与健康个体的相应水平相似或更低。当皮疹复发时,IL-8、MIP-1α、调节激活正常T细胞表达和分泌的趋化因子(RANTES)、IL-2、IFN-γ和TNF-α的转录相对水平远高于复发前,而IL-4和IL-5的mRNA相对水平未升高。每次DFPP结束时以及4次治疗后,IL-8、MIP-1α、TNF-α和IL-2的转录相对水平均低于治疗开始时。我们的观察结果表明,单核细胞产生的细胞因子和趋化因子在BP发病机制中起重要作用,其表达的调节可能与DFPP对BP的治疗效果有关。

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