Nagai Noriaki, Ito Yoshimasa, Okamoto Norio, Shimomura Yoshikazu, Okamura Haruki
Faculty of Pharmacy, Kinki University, Osaka, Japan.
J Oleo Sci. 2013;62(7):513-23. doi: 10.5650/jos.62.513.
Recent findings have implicated the involvement of interferon-γ (IFN-γ), a part of the Th1 cytokine response, in the retinal inflammation of diabetic patients. In the present study, we investigate whether hyperglycemia relates to the expression of interleukin 18 (IL-18), and leads to the production of IFN-γ in the retinas of Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. Plasma blood glucose, triglyceride and cholesterol levels in 60-week-old OLETF rats, in which the development of diabetes mellitus was observed, were significantly higher than in 60-week-old Long-Evans Tokushima Otsuka (LETO) rats used as normal controls. The expression levels of genes that cause IL-18 activation (IL-18, IL-18 receptor and caspase-1) in OLETF rats were increased at 60 weeks of age, and the levels of IL-18 and IFN-γ in 60-week-old OLETF rat retinas were also higher than in 60-week-old LETO rats. Furthermore, IFN-γ levels increased with increasing IL-18 levels in the retinas of OLETF rats, and a close relationship was observed between the levels of IL-18 and HbA1c. The rapid increase in plasma glucose levels following the oral administration of glucose solution (3.0 g/kg) did not affect the IL-18 and IFN-γ levels in the retinas of LETO rats, whereas the levels in the retinas of OLETF rats increased significantly. In conclusion, the expression of IL-18 is increased in the retinas of OLETF rats, and chronic hyperglycemia may accelerate the release of IL-18 and IFN-γ from inflammatory cells in retinal blood vessel. It is possible that IFN-γ production via IL-18 in the retinas of 60-week-old OLETF rats is caused by hyperglycemia, and plays a role in the inflammation of the OLETF rat retinas.
最近的研究结果表明，作为Th1细胞因子反应一部分的干扰素-γ（IFN-γ）参与了糖尿病患者的视网膜炎症。在本研究中，我们调查高血糖是否与白细胞介素18（IL-18）的表达有关，并导致大冢长-艾维德岛肥胖（OLETF）大鼠（一种2型糖尿病模型）视网膜中IFN-γ的产生。观察到糖尿病发生的60周龄OLETF大鼠的血浆血糖、甘油三酯和胆固醇水平显著高于用作正常对照的60周龄大冢长-艾维德岛大鼠（LETO）。OLETF大鼠中导致IL-18激活的基因（IL-18、IL-18受体和半胱天冬酶-1）的表达水平在60周龄时增加，60周龄OLETF大鼠视网膜中IL-18和IFN-γ的水平也高于60周龄LETO大鼠。此外，OLETF大鼠视网膜中IFN-γ水平随IL-18水平升高而增加，并且观察到IL-18水平与糖化血红蛋白（HbA1c）之间存在密切关系。口服葡萄糖溶液（3.0 g/kg）后血浆葡萄糖水平的快速升高对LETO大鼠视网膜中的IL-18和IFN-γ水平没有影响，而OLETF大鼠视网膜中的水平显著增加。总之，OLETF大鼠视网膜中IL-18的表达增加，慢性高血糖可能加速视网膜血管中炎症细胞释放IL-18和IFN-γ。60周龄OLETF大鼠视网膜中通过IL-18产生IFN-γ可能是由高血糖引起的，并在OLETF大鼠视网膜炎症中起作用。
