Interleukin-13 prevents autoimmune diabetes in NOD mice.
Interleukin-13 prevents autoimmune diabetes in NOD mice.
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DOI：
10.2337/diabetes.48.8.1522
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发表时间：
1999-08
期刊：
影响因子：
7.7
通讯作者：
P. Zaccone;J. Phillips;I. Conget;R. Gomis;K. Haskins;A. Minty;K. Bendtzen;A. Cooke;F. Nicoletti
中科院分区：
文献类型：
--
作者：
P. Zaccone;J. Phillips;I. Conget;R. Gomis;K. Haskins;A. Minty;K. Bendtzen;A. Cooke;F. Nicoletti
白细胞介素（IL）-13是主要由T辅助细胞（Th）-2亚群淋巴细胞产生的细胞因子，具有强大的抗炎特性。在这里，我们评估了IL-13治疗对糖尿病易感的非肥胖糖尿病（NOD）小鼠1型糖尿病发展的影响。长期使用重组人IL-13（hIL-13）治疗可显著降低小鼠自发性1型糖尿病的发病率。用hIL-13治疗的5-16周龄的雌性NOD小鼠也显示出比对照小鼠显著更轻的胰岛炎。hIL-13的预防作用与从1型到2型细胞因子应答的轻微但显著的变化相关。因此，在用伴刀豆球蛋白A离体刺激后，来自hIL-13处理的小鼠的脾淋巴样细胞（SLC）分泌的干扰素（IFN）-γ比对照少，并且在用hIL-13预处理的NOD小鼠中，抗CD 3单克隆抗体诱导的体内T细胞活化导致IFN-γ和肿瘤坏死因子-α的较低血液水平和IL-4的增加血液水平。hIL-13治疗还增加了IgE的血液水平，并抑制了1型糖尿病通过脾细胞从糖尿病供体转移到辐射受体。总之，这些数据将hIL-13添加到能够下调NOD小鼠中免疫炎症性糖尿病发生途径的细胞因子列表中，并进一步支持IL-4相关抗炎细胞因子可能在预防1型糖尿病中发挥作用的概念。
Interleukin (IL)-13 is a cytokine primarily produced by the T-helper (Th)-2 subset of lymphocytes that possesses powerful anti-inflammatory properties. Here, we have evaluated the impact of IL-13 treatment on development of type 1 diabetes in diabetes-prone nonobese diabetic (NOD) mice. Prolonged treatment with recombinant human IL-13 (hIL-13) markedly diminished the incidence of spontaneous type 1 diabetes in the mice. Female NOD mice treated from age 5-16 weeks with hIL-13 also showed significantly milder insulitis than control mice. The preventive action of hIL-13 was associated with a slight but significant change from a type 1 to a type 2 cytokine response. Accordingly, splenic lymphoid cells (SLC) from hIL-13-treated mice secreted less interferon (IFN)-gamma upon ex vivo stimulation with Concanavalin A than controls, and anti-CD3 monoclonal antibody-induced activation of T-cells in vivo resulted in lower blood levels of IFN-gamma and tumor necrosis factor-alpha and augmented blood levels of IL-4 in NOD mice pretreated with hIL-13. hIL-13 treatment also increased the blood levels of IgE and inhibited the transfer of type 1 diabetes by spleen cells from a diabetic donor to irradiated recipients. Taken together, these data add hIL-13 to the list of cytokines capable of downregulating immunoinflammatory diabetogenic pathways in NOD mice, and further support the concept that IL-4-related anti-inflammatory cytokines might have a role in the prevention of type 1 diabetes.