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人类嗜 T 淋巴细胞病毒 1 相关脊髓病/热带痉挛性截瘫(HAM/TSP)患者、人类嗜 T 淋巴细胞病毒 1 携带者和健康受试者的白细胞介素 18、白细胞介素 12 和干扰素 γ表达。

The IL-18, IL-12, and IFN-γ expression in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients, HTLV-1 carriers, and healthy subjects.

机构信息

Blood Borne Infections Research Center, Academic Center for Education, Culture and Research (ACECR), Razavi Khorasan, Mashhad, Iran.

Immunology Research Center, Inflammation and Inflammatory Diseases Division, Faculty of Medicine, Mashhad University of Medical Sciences, Azadi-Square, Medical Campus, Mashhad, 9177948564, Iran.

出版信息

J Neurovirol. 2020 Jun;26(3):338-346. doi: 10.1007/s13365-020-00832-5. Epub 2020 Apr 8.

DOI:10.1007/s13365-020-00832-5
PMID:32270468
Abstract

Interleukin (IL)-12, IL-18, and interferon gamma (IFN-γ) can induce Th1-inflammatory responses in favor of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) manifestation. In this study, the gene expression and plasma levels of these cytokines were evaluated. The peripheral blood mononuclear cells (PBMCs) in 20 HAM/TSP patients, 21 asymptomatic carriers (ACs), and 21 healthy subjects (HSs) were assessed for the expression of IL-18, IL-12, and IFN-γ, using qRT-PCR. The plasma level of IL-18 and IFN-γ were measured by an ELISA method. The mean of HTLV-1 proviral load (PVL) in the HAM/TSPs was 1846.59 ± 273.25 and higher than ACs at 719.58 ± 150.72 (p = 0.001). The IL-12 was considerably expressed only in nine ACs, five HAM/TSPs, and all HSs. Furthermore, the gene expression and plasma levels of IL-18 were lower in the HTLV-1-positive group than the control group (p = 0.001 and 0.012, respectively); however, there was no significant difference between the ACs and HAM/TSPs. The IFN-γ level was higher in the HTLV-1-positive group (p < 0.001) than HSs. Although there were no correlation between plasma levels of IL-18 and IFN-γ with PVL in the ACs, a positive correlation was observed between plasma IL-18 levels and PVL (r = 0.654, p = 0.002). The highest levels of IFN-γ were observed in the HAM/TSPs which has a significant correlation with HTLV-1-HBZ (r = 0.387, p = 0.05) but not with Tax. However, no significant correlation was found between PVL and proinflammatory pattern. Apart from the IFN-γ as a lymphokine, as a host factor, and HTLV-1-HBZ, as a viral agent, the other proinflammatory monokines or HTLV-1 factors are among the less-effective agents in the maintenance of HAM/TSP.

摘要

白细胞介素 (IL)-12、IL-18 和干扰素 γ (IFN-γ) 可诱导有利于 HTLV-1 相关脊髓病/热带痉挛性截瘫 (HAM/TSP) 表现的 Th1 炎症反应。在这项研究中,评估了这些细胞因子的基因表达和血浆水平。使用 qRT-PCR 评估了 20 名 HAM/TSP 患者、21 名无症状携带者 (AC) 和 21 名健康受试者 (HS) 的 PBMCs 中 IL-18、IL-12 和 IFN-γ 的表达。通过 ELISA 法测量 IL-18 和 IFN-γ 的血浆水平。HAM/TSP 中的 HTLV-1 前病毒载量 (PVL) 平均值为 1846.59±273.25,高于 AC 中的 719.58±150.72(p=0.001)。IL-12 仅在 9 名 AC、5 名 HAM/TSP 和所有 HS 中大量表达。此外,HTLV-1 阳性组的 IL-18 基因表达和血浆水平均低于对照组(p=0.001 和 0.012);然而,AC 和 HAM/TSP 之间没有显著差异。HTLV-1 阳性组的 IFN-γ 水平较高(p<0.001)HSs。尽管 AC 中 IL-18 和 IFN-γ 的血浆水平与 PVL 之间没有相关性,但观察到血浆 IL-18 水平与 PVL 呈正相关(r=0.654,p=0.002)。IFN-γ 水平最高的是 HAM/TSP,与 HTLV-1-HBZ 呈显著正相关(r=0.387,p=0.05),与 Tax 无关。然而,PVL 与前炎症模式之间没有发现显著相关性。除了作为淋巴因子的 IFN-γ、作为宿主因子的 HTLV-1-HBZ 和作为病毒因子的 Tax 之外,其他前炎症单克隆因子或 HTLV-1 因子也是维持 HAM/TSP 的效果较差的因素。

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