Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo 13083-865, Brazil.
Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, São Paulo 13083-865, Brazil.
Cytokine. 2018 Feb;102:55-61. doi: 10.1016/j.cyto.2017.12.006. Epub 2017 Dec 22.
Duchenne muscular dystrophy (DMD) is a progressive and fatal disease, characterized by the absence of dystrophin, muscle degeneration and cardiorespiratory failure. Creatine kinase is the classic marker to screen for DMD. However, other markers are needed to follow disease progression and to evaluate the response to therapy over longer periods. In the present study, we aim to identify interleukins in the plasma of the mdx mice model of DMD that could serve as biomarkers to monitor dystrophy progression, at distinct stages of the disease (1, 3 and 8 months of age). We used deflazacort and omega-3 therapies to validate the biomarkers studied. Plasma levels of TNF-α and TGF-β were increased in mdx mice in relation to control, at all times studied. Differences in IFN-γ and IL-10 contents, comparing mdx x CTRL, were detected only at the early stage (1 month). IL-6 decreased at 3 and 8 months and IL-13 increased at 8 months in the mdx compared to control. Deflazacort and omega-3 reduced the plasma levels of the pro-inflammatory (TNF-α, INF-γ, IL-6) and pro-fibrotic (IL-13 and TGF-β) interleukins and increased the plasma levels of IL-10. It is suggested that TNF-α and TGF-β in plasma would be the best markers to follow disease progression. IL-6, INF-γ and IL-10 would be suitable markers to the earlier stages of dystrophy and IL-13 a suitable marker to the later stages of dystrophy.
杜氏肌营养不良症(DMD)是一种进行性和致命性疾病,其特征是缺乏肌营养不良蛋白、肌肉退化和心肺衰竭。肌酸激酶是筛查 DMD 的经典标志物。然而,还需要其他标志物来跟踪疾病进展,并在更长的时间内评估治疗反应。在本研究中,我们旨在确定 DMD 的 mdx 小鼠模型血浆中的白细胞介素,这些白细胞介素可以作为监测疾病进展的生物标志物,在疾病的不同阶段(1、3 和 8 个月大)。我们使用地夫可特和 ω-3 疗法来验证所研究的生物标志物。在所有研究时间点,与对照相比,mdx 小鼠的 TNF-α 和 TGF-β 血浆水平均升高。仅在早期(1 个月)检测到 mdx x CTRL 之间 IFN-γ 和 IL-10 含量的差异。与对照相比,在 3 个月和 8 个月时,IL-6 降低,在 8 个月时 IL-13 增加。地夫可特和 ω-3 降低了促炎(TNF-α、INF-γ、IL-6)和促纤维化(IL-13 和 TGF-β)白细胞介素的血浆水平,并增加了 IL-10 的血浆水平。提示 TNF-α 和 TGF-β 可能是监测疾病进展的最佳标志物。IL-6、INF-γ 和 IL-10 可能是早期肌营养不良的合适标志物,而 IL-13 是晚期肌营养不良的合适标志物。