Laboratório de Inflamação e Imunologia das Parasitoses, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Sao Paulo, Brazil.
PLoS One. 2012;7(12):e51873. doi: 10.1371/journal.pone.0051873. Epub 2012 Dec 20.
Leukotrienes (LTs) are lipid mediators involved in several inflammatory disorders. We investigated the LT pathway in human T-lymphotropic virus type 1 (HTLV-1) infection by evaluating LT levels in HTLV-1-infected patients classified according to the clinical status as asymptomatic carriers (HACs) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients. Bioactive LTB(4) and CysLTs were both increased in the plasma and in the supernatant of peripheral blood mononuclear cell cultures of HTLV-1-infected when compared to non-infected. Interestingly, CysLT concentrations were increased in HAM/TSP patients. Also, the concentration of plasma LTB(4) and LTC(4) positively correlated with the HTLV-1 proviral load in HTLV-1-infected individuals. The gene expression levels of LT receptors were differentially modulated in CD4(+) and CD8(+) T cells of HTLV-1-infected patients. Analysis of the overall plasma signature of immune mediators demonstrated that LT and chemokine amounts were elevated during HTLV-1 infection. Importantly, in addition to CysLTs, IP-10 was also identified as a biomarker for HAM/TSP activity. These data suggest that LTs are likely to be associated with HTLV-1 infection and HAM/TSP development, suggesting their putative use for clinical monitoring.
白细胞三烯（LTs）是参与多种炎症性疾病的脂质介质。我们通过评估根据临床状态分类的人类 T 淋巴细胞白血病病毒 1（HTLV-1）感染患者（无症状携带者[HAC]和 HTLV-1 相关脊髓病/热带痉挛性截瘫[HAM/TSP]患者）的 LT 途径来研究 HTLV-1 感染中的 LT 途径。与未感染相比，生物活性 LTB（4）和 CysLTs 在 HTLV-1 感染患者的血浆和外周血单个核细胞培养上清液中均增加。有趣的是，HAM/TSP 患者的 CysLT 浓度增加。此外，血浆 LTB（4）和 LTC（4）浓度与 HTLV-1 感染者中的 HTLV-1 前病毒载量呈正相关。LT 受体的基因表达水平在 HTLV-1 感染患者的 CD4（+）和 CD8（+）T 细胞中被差异调节。对免疫介质的整体血浆特征分析表明，在 HTLV-1 感染期间 LT 和趋化因子的数量升高。重要的是，除了 CysLTs 之外，IP-10 也被确定为 HAM/TSP 活性的生物标志物。这些数据表明 LTs 可能与 HTLV-1 感染和 HAM/TSP 发展有关，提示它们可能用于临床监测。
