Hinshaw Samuel J H, Ogbeifun Osato, Wandu Wambui S, Lyu Cancan, Shi Guangpu, Li Yichao, Qian Haohua, Gery Igal
Laboratory of Immunology National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
Visual Function Core, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States.
Invest Ophthalmol Vis Sci. 2016 Mar;57(3):1441-7. doi: 10.1167/iovs.15-19040.
Digoxin, a major medication for heart disease, was recently reported to have immunosuppressive capacity. Here, we determined the immunosuppressive capacity of digoxin on the development of experimental autoimmune uveitis (EAU) and on related immune responses.
The B10.A mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) and were treated daily with digoxin or vehicle control. On postimmunization day 14, the mouse eyes were examined histologically, while spleen cells were tested for cytokine production in response to IRBP and purified protein derivative. The immunosuppressive activity of digoxin was also tested in vitro, by its capacity to inhibit development of Th1 or Th17 cells. To investigate the degenerative effect of digoxin on the retina, naïve (FVB/N × B10.BR)F1 mice were similarly treated with digoxin and tested histologically and by ERG.
Treatment with digoxin inhibited the development of EAU, as well as the cellular response to IRBP. Unexpectedly, treatment with digoxin suppressed the production of interferon-γ to a larger extent than the production of interleukin 17. Importantly, digoxin treatment induced severe retinal degeneration, determined by histologic analysis with thinning across all layers of the retina. Digoxin treatment also induced dose-dependent vision loss monitored by ERG on naïve mice without induction of EAU.
Treatment of mice with digoxin inhibited the development of EAU and cellular immune response to IRBP. However, the treatment induced severe damage to the retina. Thus, the use of digoxin in humans should be avoided due to its toxicity to the retina.
地高辛是一种治疗心脏病的主要药物，最近有报道称其具有免疫抑制能力。在此，我们确定了地高辛对实验性自身免疫性葡萄膜炎（EAU）的发展及相关免疫反应的免疫抑制能力。
用视网膜间视黄醇结合蛋白（IRBP）免疫B10.A小鼠，并每日用地高辛或溶剂对照进行处理。在免疫后第14天，对小鼠眼睛进行组织学检查，同时检测脾细胞对IRBP和纯化蛋白衍生物的细胞因子产生情况。还通过地高辛抑制Th1或Th17细胞发育的能力在体外测试其免疫抑制活性。为研究地高辛对视网膜的退行性影响，用类似方法处理未免疫的（FVB/N×B10.BR）F1小鼠，进行组织学检查和视网膜电图（ERG）检测。
地高辛治疗可抑制EAU的发展以及对IRBP的细胞反应。出乎意料的是，地高辛治疗对γ干扰素产生的抑制程度大于白细胞介素17。重要的是，通过组织学分析确定地高辛治疗导致严重的视网膜变性，视网膜各层均变薄。地高辛治疗还导致未诱导EAU的未免疫小鼠出现剂量依赖性视力丧失，通过ERG监测。
地高辛治疗小鼠可抑制EAU的发展及对IRBP的细胞免疫反应。然而，该治疗导致视网膜严重受损。因此，由于地高辛对视网膜有毒性，应避免在人类中使用。
