Institute of Disease Control and Prevention, Academy of Military Medical Science, Beijing 100071, China.
Virol J. 2010 Feb 9;7:30. doi: 10.1186/1743-422X-7-30.
Influenza is a respiratory disease that seriously threatens human health. In fact, influenza virus itself does not make critical contribution to mortality induced by influenza, but "cytokine storm" produced by the excessive immune response triggered by the virus can result in inflammatory reaction of lung tissues and fatal lung tissue injury, and thus increase influenza mortality. Therefore, besides antiviral drugs, immunosuppression drugs should also be included in infection treatment.
Complement is the center of inflammatory reaction. If complement system is over activated, the body will have strong inflammatory reaction or tissue injury, resulting in pathological process. Many studies have proved that, inflammatory injury of lung tissues caused by influenza virus is closely related to complement activation. Therefore, inhibiting complement activation can significantly reduce inflammatory injury in lung tissues. As complement is both a physiological defense and pathological damage medium, systematic inhibition may result in side effects including infection. Therefore, we design targeting complement inhibitors for complement activation sites, i.e. with CR2 as targeting vector, complement inhibitors like CD59 and Crry are targeted to inflammatory sites to specially inhibit the complement activation in local injury, thus local inflammatory reaction is inhibited.
CR2-CD59 and CR2-Crry targeting complement inhibitors are fusion-expressed, and their biological activity is examined via in vivo and in vitro tests. CR2 targeting complement inhibitors are used to treat mouse influenza viral pneumonia model, with PBS treatment group as the control. The survival and lung tissue injury of the mice is observed and the effect of CR2 targeting complement inhibitors on pneumonia induced by influenza virus is evaluated.
CR2 targeting complement inhibitors are expected to be ideal drugs for viral pneumonia.
流感是一种严重威胁人类健康的呼吸道疾病。事实上，流感病毒本身并不会对流感引起的死亡率做出重大贡献，而是病毒引发的过度免疫反应产生的“细胞因子风暴”，会导致肺部组织炎症反应和致命的肺组织损伤，从而增加流感的死亡率。因此，除了抗病毒药物外，免疫抑制剂也应该包括在感染治疗中。
补体是炎症反应的中心。如果补体系统过度激活，机体将发生强烈的炎症反应或组织损伤，导致病理过程。许多研究已经证明，流感病毒引起的肺部组织炎症损伤与补体激活密切相关。因此，抑制补体激活可以显著减轻肺部组织的炎症损伤。由于补体既是生理防御又是病理损伤的介质，系统性抑制可能会导致包括感染在内的副作用。因此，我们设计了针对补体激活部位的靶向补体抑制剂，即使用 CR2 作为靶向载体，将补体抑制剂如 CD59 和 Crry 靶向炎症部位，专门抑制局部损伤中的补体激活，从而抑制局部炎症反应。
CR2-CD59 和 CR2-Crry 靶向补体抑制剂进行融合表达，并通过体内和体外试验检测其生物学活性。使用 CR2 靶向补体抑制剂治疗小鼠流感病毒性肺炎模型，以 PBS 治疗组作为对照。观察小鼠的存活和肺组织损伤情况，并评估 CR2 靶向补体抑制剂对流感病毒引起的肺炎的作用。
CR2 靶向补体抑制剂有望成为病毒性肺炎的理想药物。
