干扰素在体外引起细胞抗病毒状态的动力学变化

KINETICS OF ANTIVIRAL STATE IN CELLS ACTIVATED BY INTERFERON IN VITRO

干扰素(INF-α和β)引起细胞的抗病毒状态出现很快,6～7h后即可完全保护细胞.该状态在洗去IFN后可保持9～12h,48h后仍有一定的保护作用.IFN-γ与IFN-α和β不同,它引起细胞的抗病毒状态要慢得多,24h后才能完全保护细胞.比较三种浓度的IFN-α时,可见5IU/ml不能完全保护细胞,而250IU/ml和25IU/ml时的抗病毒状态的动力学变化是一致的.该病毒状态可被加入的抗IFN-α血清抑制,但必须在该状态形成前加入.这些结果对临床工作者在制订治疗方案时将是有用的参考.

In order to rationalize the clinical use of interferon (IFN), we observed the kinetics of antiviral state in cells activated by IFN. In experiments we adopted microplate dye-binding assay originally used to measure the titer of IFN and natural HuIFN-α,-βand-γ,Assay cells of A549 cell line were used.challenge virus was vesicular stomatitis virus (VSV).Cells were cultured to confluence in wells of plate,IFN was added to four wells in each time at various intervals,then washed five times and challenged with VSV.After 24-32 hrs,the dye was added and OD values Were measured.In order to determine the duration of antiviral state,IFN was kept on cells until the antiviral state was fully developed,then washed at various intervals and challenged. The development of antiviral state in cells activated by IFN-αand-β was quite rapid.After 6-7 hrs of treatment it could protect cells completely,and the protective action was maintained for another 9-12 hrs after washing.Then it declined and there was still some protective effect after 48 hrs.IFN-γ was very different from IFN-α and-β.It activated cells much more slowly,and could protect cells completely only after 24 hrs of treatment.The cells could not be protected completely by IFN-α in 5 IU/ml,and the kinetics were similar in 250 and 25 IU/ml.The antiviral state was inhibited,when anti-IFN-α serum was added before its development.These results showed that in the clinical use of different kinds of IFN,it might not be necessary to use maximal tolerated doses and daily administrations,and to keep a high level of IFN in blood for a long time.