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宿主对米氮平治疗的人源化皮肤利什曼病无反应和有反应患者的免疫反应:Th1 和 Th2 途径的病例对照研究。

Host's immune response in unresponsive and responsive patients with anthroponotic cutaneous leishmaniasis treated by meglumine antimoniate: A case-control study of Th1 and Th2 pathways.

机构信息

Research Center of Tropical and Infectious Diseases, Kerman University of Medical Sciences, Kerman, Iran.

Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.

出版信息

Int Immunopharmacol. 2019 Apr;69:321-327. doi: 10.1016/j.intimp.2019.02.008. Epub 2019 Feb 14.

DOI:10.1016/j.intimp.2019.02.008
PMID:30771740
Abstract

The objective of the present study was to compare the host's immune responses between unresponsive and responsive patients with anthroponotic cutaneous leishmaniasis (ACL) treated by meglumine antimoniate. A case-control study was carried out in an endemic focus in Iran. Blood samples were taken from patients and peripheral blood mononuclear cells (PBMCs) were isolated. Two wells were considered for each isolate of unresponsive and responsive patients; one was exposed to L. tropica (Lt-stimulated cells) and the other remained non-exposed (non-stimulated cells). After 24 h of incubation, whole RNA was extracted from each sample. Real-time quantitative PCR was carried out to confirm the differences in expression levels of IL-12 P40, IFN-γ, IL-1β, IL-4 and IL-10 among isolates. Data were analyzed and P < 0.05 was considered to be statistically significant. In our study, Lt-stimulated cells and non-stimulated cells in unresponsive groups demonstrated significantly lower expression levels of IL-1β, IL-12 P40 and IFN-γ genes and higher expression levels of IL-4 and IL-10 genes, compared to Lt-stimulated cells and non-stimulated cells in responsive groups. There was a negative correlation between IL-12 P40 with IL-10 and IL-1β with IL-10 in ACL Lt-stimulated cells in unresponsive group, while a positive correlation between IL-12 P40 with IL-1β and IL-12 P40 with IFN-γ in ACL Lt-stimulated cells in responsive group. Probably, different immune responses caused by various factors play a major role in the pathogenesis and development of unresponsiveness in ACL patients. The profile and timing of cytokine production correlated well with the treatment outcome of Leishmania infection.

摘要

本研究的目的是比较用葡甲胺锑治疗无反应和有反应的人源化皮肤利什曼病(ACL)患者的宿主免疫反应。在伊朗的一个流行地区进行了病例对照研究。从患者中采集血液样本,并分离外周血单核细胞(PBMC)。为无反应和有反应患者的每个分离物考虑两个孔;一个暴露于 L. tropica(Lt 刺激细胞),另一个保持未暴露(非刺激细胞)。孵育 24 小时后,从每个样品中提取总 RNA。进行实时定量 PCR 以确认 IL-12 P40、IFN-γ、IL-1β、IL-4 和 IL-10 在分离物中的表达水平差异。对数据进行分析,P < 0.05 被认为具有统计学意义。在我们的研究中,与有反应组的 Lt 刺激细胞和非刺激细胞相比,无反应组的 Lt 刺激细胞和非刺激细胞中 IL-1β、IL-12 P40 和 IFN-γ 基因的表达水平显著降低,而 IL-4 和 IL-10 基因的表达水平更高。在无反应组的 ACL Lt 刺激细胞中,IL-12 P40 与 IL-10 和 IL-1β 与 IL-10 之间呈负相关,而在有反应组的 ACL Lt 刺激细胞中,IL-12 P40 与 IL-1β 和 IL-12 P40 与 IFN-γ 之间呈正相关。可能是由于各种因素引起的不同免疫反应在 ACL 患者无反应的发病机制和发展中起主要作用。细胞因子产生的特征和时间与利什曼原虫感染的治疗结果密切相关。

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