重组集成干扰素α在不同动物长期毒性实验血清中中和抗体的产生及活性研究

目的研究重组集成干扰素α在金黄地鼠和猕猴长期毒性实验血清中中和抗体的产生及抗体活性的强弱。方法将金黄地鼠与猕猴分别分为10、30、100μg/kg与1、10、100μg/kg3个剂量组,均每日皮下注射重组集成干扰素α1次,各连续用药60、30d,取给药期和恢复期不同时间的血清,采用细胞病变抑制法进行检测。结果金黄地鼠的30、100μg/kg剂量组与猕猴的3个剂量组从给药第3wk起,在血清中检测到具有中和活性的抗体,抗体滴度在给药第4wk或恢复期第1wk达最高峰,并持续到恢复期结束。其中,猕猴10、100μg/kg剂量组的中和活性高于同期1μg/kg剂量组,10、100μg/kg剂量组之间则无显著性差异(P>0.05),1μg/kg剂量组在恢复期结束时已检测不到中和活性。结论金黄地鼠和猕猴重复注射重组集成干扰素α,血清中均能检测到中和抗体(低剂量组除外),抗体滴度和持续时间与注射剂量呈正相关。

Production and Activity of Serum Neutralizing Antibody in Different Animals Undergoing Long- term Toxicity Study with Recombinant Consensus Interferon α

OBJECTIVE:To investigate the production and activity of serum neutralizing antibody in normal rhesus monkeys and hamsters undergoing long-term toxicity study with recombinant consensus interferonα.METHODS:The hamsters were administrated subcutaneously(S.C)with IFN-Conαat dosages of10,30and100μg/kg,respectively for60days;and the rhesus monkeys were treated S.C with IFN-Conαat dosages of1,10and100μg/kg,respectively for30days.Anti-IFN-Conαantibodies and their neutralizing activities in serum samples taken at different times after administration and at different stage of recovery were determined using the cytopathic-effect inhibition assay.RESULTS:On the3rd week of administration,anti-IFN-Conαantibodies with neutralizing activities were detected in hamsters at30and100μg/kg dosage groups and in all the3dosage subgroups of rhesus monkeys.Antibody titer reached to the peak on the4th week of administration or on the1st week on the recovery stage and remained till the end of convalescent period.Neutralizing activity for Rhesus monkeys at10and100μg/kg dosages was higher than that at1μg/kg dosage,but there was no significant difference between10and100μg/kg dosages(P>0.05).In1μg/kg dosage group,no neutralizing activity was detected at the end of convalescent period.CONCLUSION:The neutralizing antibodies can be detected in the serum of both hamsters and rhesus monkeys after repeating injection of recombinant consensus interferonα.The titers of antibody are in direct ratio with the duration and the injected dose.