Wyde P R, Wilson S Z, Kramer M J, Sun C S, Knight V
Antimicrob Agents Chemother. 1984 Jun;25(6):729-34. doi: 10.1128/AAC.25.6.729.
Small particle aerosols of a hybrid DNA recombinant human alpha interferon, A/D bgl, and a related DNA recombinant leukocyte interferon, A, were generated and delivered to mice for 23.5 h a day for 4 consecutive days. The antiviral activity of these interferons in delivery reservoirs, in the aerosols generated, and in the lungs of test mice was monitored during and after aerosol administration in cytopathic effect inhibition assays, using vesicular stomatitis virus as the indicator virus. In addition, the activity of these interferons in primary mouse embryo cells against influenza A/HK/68 (H3N2) virus was determined. The results obtained indicated that the interferon particles generated in the continuous aerosol therapy system used in these studies remained biologically active and could be readily detected in both aerosol mists and lungs of test mice; levels of exogenous interferon in the lungs equalled or exceeded levels of interferons produced endogenously during experimentally induced influenza virus infection. Titers of the exogenously administered interferons decreased gradually and disappeared from the lungs between 24 and 48 h after cessation of aerosolization. Recombinant human alpha interferon A/D, but not recombinant leukocyte alpha interferon A, significantly inhibited replication of A/HK/68 virus in primary mouse embryo cells in the in vitro studies.
制备了一种杂交DNA重组人α干扰素A/D bgl的小颗粒气溶胶以及一种相关的DNA重组白细胞干扰素A，并将其输送给小鼠，每天23.5小时，连续4天。在细胞病变效应抑制试验中，以水泡性口炎病毒作为指示病毒，在气溶胶给药期间和之后，监测这些干扰素在输送储器、所产生的气溶胶以及受试小鼠肺中的抗病毒活性。此外，还测定了这些干扰素在原代小鼠胚胎细胞中对甲型流感病毒A/HK/68（H3N2）的活性。所获得的结果表明，在这些研究中使用的连续气溶胶治疗系统中产生的干扰素颗粒保持生物活性，并且在气溶胶雾滴和受试小鼠的肺中都能很容易地检测到；肺中外源干扰素的水平等于或超过实验性诱导流感病毒感染期间内源性产生的干扰素水平。在停止雾化后24至48小时之间，外源给予的干扰素滴度逐渐降低并从肺中消失。在体外研究中，重组人α干扰素A/D，而不是重组白细胞α干扰素A，能显著抑制原代小鼠胚胎细胞中A/HK/68病毒的复制。
