鞭毛蛋白衍生多肽CBLB502免疫反应对其抗辐射作用的影响

Effects of immunoreaction by flagellin derived polypeptide CBLB502 on its radioprotection in mice

目的 Toll样受体5(TLR5)配体鞭毛蛋白衍生多肽CBLB502,具有良好的辐射防护作用,但其本身具有一定的免疫激活作用。该文拟研究CBLB502的免疫原性对其抗辐射药效的影响。方法应用ELISA方法检测正常人群中CBLB502的免疫原性反应,通过CBLB502对小鼠的迟发型超敏反应和溶血空斑实验,观察多次免疫小鼠对CBLB502的免疫反应以及对其抗辐射活性的影响。结果约4.5%正常人对CBLB502具有较高反应性,CBLB502较高剂量时(10 mg/kg)小鼠迟发型超敏反应增强,体液免疫受到抑制;但在较低剂量(<3 mg/kg)时无免疫毒性。连续给药可显著激活小鼠的免疫反应,但对CBLB502的抗辐射活性抑制达80%~90%,显著降低小鼠存活率。此外,高剂量(0.5 mg/kg)给药组的存活率显著低于免疫照射对照组。结论 CBLB502连续给药可显著降低其抗辐射活性并具有一定副作用。

Objective To investigate the effects of immunogenicity of CBLB502 on the radioprotective activity. Methods The immunogenicity in normal human populations was examined using ELISA,the delayed type hypersensitivity and hemolytic plaque assay were performed in mice,and the effects of hyperimmune response on radioprotection of CBLB502 were observed using multiple immunized mice. Results About 4.5% of normal populations were hyper-responsive against CBLB502,and CBLB502 increased delayed hypersensitivity,but inhibited the humoral immunity at a higher dose(10 mg/kg body weight). However,there was no obvious immunotoxicity at a lower dose(<3 mg/kg). Continuous immune stimulation could significantly enhance mouse immunoreaction,but reduce radioprotective activity by 80%-90%,and obviouly decrease the mouse survival. High doses(0.5 mg/kg)might cause more mortality than among irradiated immune stimulating mice. Conclusion Taken together,these results indicate that multiple administration of CBLB502 might reduce its radioprotective activity and has side effects.