Faculty of Medicine, University of New South Wales, Sydney, Australia.
Diabetes. 2012 Jun;61(6):1500-8. doi: 10.2337/db11-0264. Epub 2012 Apr 3.
Cytokines are upregulated in prediabetes, but their relationship with Enterovirus (EV) infection and development of islet autoimmunity is unknown. Cytokines (n = 65) were measured using Luminex xMAP technology in a nested case-control study of 67 children with a first-degree relative with type 1 diabetes: 27 with islet autoantibodies (Ab(+)) and 40 age-matched persistently autoantibody negative (Ab(-)) control subjects. Of 74 samples, 37 (50%) were EV-PCR(+) in plasma and/or stool (EV(+)) and the remainder were negative for EV and other viruses (EV(-)). Fifteen cytokines, chemokines, and growth factors were elevated (P ≤ 0.01) in Ab(+) versus Ab(-) children (interleukin [IL]-1β, IL-5, IL-7, IL-12(p70), IL-16, IL-17, IL-20, IL-21, IL-28A, tumor necrosis factor-α, chemokine C-C motif ligand [CCL]13, CCL26, chemokine C-X-C motif ligand 5, granulocyte-macrophage colony-stimulating factor, and thrombopoietin); most have proinflammatory effects. In EV(+) versus EV(-) children, IL-10 was higher (P = 0.005), while IL-21 was lower (P = 0.008). Cytokine levels did not differ between Ab(+)EV(+) and Ab(+)EV(-) children. Heat maps demonstrated clustering of some proinflammatory cytokines in Ab(+) children, suggesting they are coordinately regulated. In conclusion, children with islet autoimmunity demonstrate higher levels of multiple cytokines, consistent with an active inflammatory process in the prediabetic state, which is unrelated to coincident EV infection. Apart from differences in IL-10 and IL-21, EV infection was not associated with a specific cytokine profile.
细胞因子在糖尿病前期上调，但它们与肠道病毒 (EV) 感染和胰岛自身免疫的发展的关系尚不清楚。在一项针对 67 名一级亲属患有 1 型糖尿病的儿童的巢式病例对照研究中，使用 Luminex xMAP 技术测量了细胞因子 (n = 65)：27 名胰岛自身抗体 (Ab(+))和 40 名年龄匹配的持续自身抗体阴性 (Ab(-))对照。在 74 个样本中，37 个（50%）在血浆和/或粪便中 EV-PCR(+)（EV(+))，其余为 EV 和其他病毒阴性（EV(-))。15 种细胞因子、趋化因子和生长因子在 Ab(+)儿童中升高（P ≤ 0.01）与 Ab(-)儿童（白细胞介素 [IL]-1β、IL-5、IL-7、IL-12(p70)、IL-16、IL-17、IL-20、IL-21、IL-28A、肿瘤坏死因子-α、趋化因子 C-C 基序配体 [CCL]13、CCL26、趋化因子 C-X-C 基序配体 5、粒细胞-巨噬细胞集落刺激因子和血小板生成素）；大多数具有促炎作用。在 EV(+)与 EV(-)儿童中，IL-10 更高（P = 0.005），而 IL-21 更低（P = 0.008）。Ab(+)EV(+)和 Ab(+)EV(-)儿童的细胞因子水平没有差异。热图显示 Ab(+)儿童中一些促炎细胞因子聚类，表明它们是协调调节的。总之，患有胰岛自身免疫的儿童表现出多种细胞因子水平升高，这与糖尿病前期状态下的活跃炎症过程一致，与同时发生的 EV 感染无关。除了 IL-10 和 IL-21 的差异外，EV 感染与特定的细胞因子谱无关。
