A. I. Virtanen Institute, University of Eastern Finland, Kuopio, Finland.
J Neuroinflammation. 2012 May 29;9:105. doi: 10.1186/1742-2094-9-105.
Human intravenous immunoglobulin (hIVIG) preparation is indicated for treating primary immunodeficiency disorders associated with impaired humoral immunity. hIVIG is known for its anti-inflammatory properties and a decent safety profile. Therefore, by virtue of its constituent natural anti-amyloid beta antibodies and anti-inflammatory effects, hIVIG is deemed to mediate beneficial effects to patients of Alzheimer's disease (AD). Here, we set out to explore the effects of hIVIG in a mouse model of AD.
We treated APP/PS1dE9 transgenic and wild-type mice with weekly injections of a high hIVIG dose (1 g/kg) or saline for 3 or 8 months. Treatment effect on brain amyloid pathology and microglial reactivity was assessed by ELISA, immunohistochemistry, RT-PCR, and confocal microscopy.
We found no evidence for reduction in Aβ pathology; instead 8 months of hIVIG treatment significantly increased soluble levels of Aβ40 and Aβ42. In addition, we noticed a significant reduction in CD45 and elevation of Iba-1 markers in specific sub-populations of microglial cells. Long-term hIVIG treatment also resulted in significant suppression of TNF-α and increase in doublecortin positive adult-born neurons in the dentate gyrus.
Our data indicate limited ability of hIVIG to impact amyloid burden but shows changes in microglia, pro-inflammatory gene expression, and neurogenic effects. Immunomodulation by hIVIG may account for its beneficial effect in AD patients.
人静脉注射免疫球蛋白（hIVIG）制剂用于治疗与体液免疫受损相关的原发性免疫缺陷疾病。hIVIG 以其抗炎特性和良好的安全性而闻名。因此，由于其包含的天然抗淀粉样β抗体和抗炎作用，hIVIG 被认为对阿尔茨海默病（AD）患者具有有益的影响。在这里，我们着手研究 hIVIG 在 AD 小鼠模型中的作用。
我们用每周一次 1g/kg 的高 hIVIG 剂量或生理盐水对 APP/PS1dE9 转基因和野生型小鼠进行治疗，持续 3 或 8 个月。通过 ELISA、免疫组织化学、RT-PCR 和共聚焦显微镜评估治疗对脑淀粉样蛋白病理学和小胶质细胞反应性的影响。
我们没有发现 hIVIG 治疗可减少 Aβ 病理学的证据；相反，8 个月的 hIVIG 治疗显著增加了可溶性 Aβ40 和 Aβ42 的水平。此外，我们注意到特定小胶质细胞亚群中的 CD45 和 Iba-1 标志物显著减少。长期 hIVIG 治疗还导致 TNF-α 的显著抑制和齿状回中双皮质素阳性成体神经元的增加。
我们的数据表明 hIVIG 对淀粉样蛋白负荷的影响有限，但显示出小胶质细胞、促炎基因表达和神经发生效应的变化。hIVIG 的免疫调节可能解释了其在 AD 患者中的有益作用。
