Talcott P A, Koller L D, Woodard L F, Whitbeck G A
Int J Immunopharmacol. 1986;8(6):553-9. doi: 10.1016/0192-0561(86)90025-1.
Tumor growth and regression was studied in C57BL/6J mice injected with Moloney sarcoma virus (MSV) and treated with the interferon (IFN)-inducing drug, avridine. Avridine decreased the persistence of tumors when given one or five days after virus, but shortened the prepatent period and increased persistence if given one day prior to virus. Additional studies were undertaken to study the role that serum interferon and natural killer (NK) cell activity might have in this phenomenon. Interferon levels were greatly enhanced (over that induced by virus alone or avridine alone) when avridine was given one day after, but not one day before, virus. Six days after viral infection, interferon titers had returned to near zero but could be boosted by injecting avridine at day 5. Multiple injections of avridine before and after virus resulted in refractoriness to interferon induction and tumor persistence. NK activity was greatly increased by virus at two days post-infection, and avridine given one day after infection significantly enhanced cytotoxicity of these splenic cells against tumor cells. By six days after infection, NK activity had returned to normal but could be increased by avridine given at five days post-infection. It appeared that high levels of interferon induced by avridine given at one or five days after infection increased NK activity and may have been responsible for enhanced regression. Pre-treatment by avridine had little effect on interferon levels over that induced by virus alone, but that did not explain the enhancement of tumor growth since NK activity was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
在注射莫洛尼肉瘤病毒(MSV)并用诱导干扰素(IFN)的药物阿夫立定治疗的C57BL/6J小鼠中研究了肿瘤的生长和消退情况。在病毒感染后1天或5天给予阿夫立定可降低肿瘤的持续时间,但如果在病毒感染前1天给予,则会缩短潜伏期并增加肿瘤持续时间。还进行了额外的研究,以探讨血清干扰素和自然杀伤(NK)细胞活性在这一现象中可能发挥的作用。当在病毒感染后1天而非前1天给予阿夫立定,干扰素水平会大幅提高(超过单独由病毒或阿夫立定诱导的水平)。病毒感染6天后,干扰素滴度已降至接近零,但在第5天注射阿夫立定可使其升高。在病毒感染前后多次注射阿夫立定导致对干扰素诱导和肿瘤持续存在产生抗性。感染后2天,病毒可使NK活性大幅增加,感染后1天给予阿夫立定可显著增强这些脾细胞对肿瘤细胞的细胞毒性。到感染后6天,NK活性已恢复正常,但在感染后5天给予阿夫立定可使其增加。似乎在感染后1天或5天给予阿夫立定诱导的高水平干扰素增加了NK活性,这可能是肿瘤消退增强的原因。阿夫立定预处理对干扰素水平的影响不大,仅略高于单独由病毒诱导的水平,但这并不能解释肿瘤生长的增强,因为NK活性增加了。(摘要截短至250字)