Increased expression of IL-18 in the serum and islets of type 1 diabetics
Increased expression of IL-18 in the serum and islets of type 1 diabetics
复制标题
DOI：
10.1016/j.molimm.2014.12.012
复制
发表时间：
2015-04-01
影响因子：
3.6
通讯作者：
Sarvetnick, Nora E.
中科院分区：
文献类型：
--
作者：
Harms, Robert Z.;Yarde, Danielle N.;Sarvetnick, Nora E.
1 型糖尿病 (T1D) 是一种慢性疾病，其特征是自身免疫介导的胰腺产生胰岛素的 β 细胞遭到破坏。白细胞介素 (IL)-18 是一种促炎细胞因子，与许多炎症性疾病的发病机制有关。在这里，我们分析了 1 型糖尿病青少年血浆中 IL-18 的水平。与对照组相比，1 型糖尿病患者的 IL-18 水平显着升高。另一方面，将 T1D 与对照样本进行比较时，IL-18 功能的两种负调节因子 IL-18 结合蛋白 (IL-18BP) 和 IL-37 的水平保持不变。然而值得注意的是，尽管 IL-18BP 水平没有升高，但发现 IL-18 和 IL-18BP 在 1 型糖尿病患者中呈正相关。即便如此，糖尿病患者中游离的、未结合的 IL-18 仍然显着增加。此外，相关性研究还显示，IL-18 和 IL-18BP 与 T1D 患者的 HbA1c 水平呈正相关，表明 IL-18 与这些患者的代谢控制之间存在潜在联系。最后，我们观察到从 1 型糖尿病患者采集的人胰岛标本中 IL-18 蛋白表达显着增加。这些结果进一步扩展了我们对 IL-18 在 T1D 中作用的认识，可能有助于深入了解与 T1D 和 T2D 代谢控制相关的常见致病机制，并表明针对这种细胞因子可能会改善 T1D 患者的治疗结果。 (C) 2015 Elsevier Ltd. 保留所有权利。
Type 1 diabetes (T1D) is a chronic disease characterized by autoimmune-mediated destruction of pancreatic insulin-producing beta cells. Interleukin (IL)-18 is a pro-inflammatory cytokine implicated in the pathogenesis of a number of inflammatory diseases. Here, we analyzed IL-18 levels in the plasma of juveniles with T1D. Compared to control subjects, IL-18 levels were significantly elevated in patients with T1D. On the other hand, levels of IL-18 binding protein (IL-18BP) and IL-37, two negative regulators of IL-18 function, remained unchanged when comparing T1D to control samples. Notably, however, although IL-18BP levels were not elevated, IL-18 and IL-18BP were found to be positively correlated in type 1 diabetics. Even so, free, unbound IL-18 remained significantly increased in diabetic patients. Additionally, correlation studies also revealed that IL-18 and IL-18BP are positively correlated with HbA1c levels in T1D patients, suggesting a potential link between IL-18 and metabolic control in these patients. Finally, we observed a significant increase in IL-18 protein expression within human pancreatic islet specimens collected from type 1 diabetics. These results further expand our knowledge of the role of IL-18 in T1D, may give insight into common pathogenic mechanisms associated with metabolic control in both T1D and T2D, and suggest that targeting this cytokine may improve therapeutic outcomes for T1D patients. (C) 2015 Elsevier Ltd. All rights reserved.