Human intravenous immune globulin (IVIg), a purified IgG fraction composed of ~ 60% IgG1 and obtained from the pooled plasma of thousands of donors, is clinically used for a wide range of diseases. The biological actions of IVIg are incompletely understood and have been attributed both to the polyclonal antibodies therein and also to their IgG (IgG) Fc regions. Recently, we demonstrated that multiple therapeutic human IgG1 antibodies suppress angiogenesis in a target-independent manner via FcγRI, a high-affinity receptor for IgG1. Here we show that IVIg possesses similar anti-angiogenic activity and inhibited blood vessel growth in five different mouse models of prevalent human diseases, namely, neovascular age-related macular degeneration, corneal neovascularization, colorectal cancer, fibrosarcoma and peripheral arterial ischemic disease. Angioinhibition was mediated by the Fc region of IVIg, required FcγRI and had similar potency in transgenic mice expressing human FcγRs. Finally, IVIg therapy administered to humans for the treatment of inflammatory or autoimmune diseases reduced kidney and muscle blood vessel densities. These data place IVIg, an agent approved by the US Food and Drug Administration, as a novel angioinhibitory drug in doses that are currently administered in the clinical setting. In addition, they raise the possibility of an unintended effect of IVIg on blood vessels.

中文翻译：

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静脉内免疫球蛋白可抑制小鼠和人类的血管生成。

人静脉内免疫球蛋白（IVIg）是由约60％IgG1组成的纯化IgG组分，得自数千名捐献者的合并血浆，在临床上被广泛用于多种疾病。IVIg的生物学作用尚不完全清楚，不仅归因于其中的多克隆抗体，还归因于其IgG（IgG）Fc区。最近，我们证明了多种治疗性人类IgG1抗体可通过FcγRI（一种IgG1的高亲和力受体）以靶标独立的方式抑制血管生成。在这里，我们显示，IVIg在人类疾病的五种不同小鼠模型中具有相似的抗血管生成活性，并抑制了血管的生长，这些模型包括与年龄有关的新血管性黄斑变性，角膜新生血管，结直肠癌，纤维肉瘤和周围动脉缺血性疾病。血管抑制作用由IVIg的Fc区介导，是必需的FcγRI，在表达人FcγR的转基因小鼠中具有相似的效力。最后，施用于人类的IVIg疗法可治疗炎症性或自身免疫性疾病，从而降低了肾脏和肌肉的血管密度。这些数据使IVIg（一种由美国食品和药物管理局批准的药物）成为一种新型的血管抑制药物，其剂量目前在临床环境中使用。此外，它们增加了IVIg对血管产生意想不到的作用的可能性。这些数据使IVIg（一种由美国食品和药物管理局批准的药物）成为一种新型的血管抑制药物，其剂量目前在临床环境中使用。此外，它们增加了IVIg对血管产生意想不到的作用的可能性。这些数据使IVIg（一种由美国食品和药物管理局批准的药物）成为一种新型的血管抑制药物，其剂量目前在临床环境中使用。此外，它们增加了IVIg对血管产生意想不到的作用的可能性。