重组人IL-6对NOD小鼠IDDM发病的影响及机制研究

目的　探讨重组人白细胞介素 6(rhIL 6)对NOD小鼠自发性和环磷酰胺 (CY)诱发性Ⅰ型糖尿病 (IDDM)的影响及相关机制。方法　通过观察NOD小鼠用药后血糖和尿糖水平、胰腺组织病理学特征 ,及血清抗CD3抗体、LPS诱导的炎症因子IFN γ、TNF α水平的变化 ,以及CY诱导ID DM发生率 ,确定rhIL 6的抗IDDM作用。结果　 4wk龄♀NOD小鼠连续注射rhIL 6 1 6wk后 ,胰岛炎即胰腺淋巴细胞、单核细胞浸润明显减少 ,糖尿病的发病率明显降低(33 % )。与空白对照组相比 ,血清中炎症因子IFN γ、TNF α水平也呈显著的下降趋势。 1 2wk龄NOD小鼠连续 8wk应用rhIL 6 ,糖尿病发生率则无明显变化 ,且实验中未观察到rhIL 6对CY诱发IDDM的保护作用。结论　rhIL 6早期预防用药可降低NOD小鼠自发性IDDM的发生 ,该保护作用可能与其降低炎症因子TNF α、IFN γ分泌有关

The effects of interleukin-6 on the development of autoimmune diabetes in NOD mouse

AIM To investigate the anti-inflammatory properties of IL-6 on the development of IDDM(insulin dependent diabetes mellitus) in NOD mouse. METHODS IL-6 was administered exogenously in female NOD mice (spontaneous model) and cyclophosphamide-treated NOD mice (accelerated model) respectively. During the study period, the mice were evaluated for development of diabetes once a week. At the end of experiment, 8 euglycosuria mice from each group were sacrificed for histoimmunological analysis, and the production of TNF-α and IFN-γ from spleen lymphoid cells were detected. RESULTS The incidence of IDDM in spontaneous model(33%) were significantly reduced after 12 weeks of treatment. TNF-α(P<0.01) and IFN-γ(P<0.01) were decreased obviously. CONCLUSION IL-6 protected rodent models against IDDM, which was accompanied by a dramatic reduction of TNF-α and IFN-γ production, suggesting that inhibiting the secretion of these cytokine might be a pivotal mechanism by which IL-6 exerts its anti-inflammation effects.