Kimberlin R H, Walker C A
Institute for Animal Health, AFRC & MRC Neuropathogenesis Unit, Edinburgh, Scotland.
Arch Virol. 1990;112(1-2):103-14. doi: 10.1007/BF01348988.
Single intraperitoneal (i.p.) doses of 16 different drugs were given to mice 2 h before injecting scrapie i.p. Scrapie was injected as serial ten-fold dilutions of standard inocula and the effective titres obtained were used as a measure of the relative efficiency of infection in treated compared to saline injected mice. Despite the wide variety of drugs tested, most of them increased, non-specifically, the efficiency of infection by 0.6 to 2.1 log10 i.p. LD50 units (i.e., 4 to 126-fold), but only when both drug and scrapie were given i.p. The effect was greatest with a 2 h or a 6 h interval suggesting an involvement either of resident peritoneal cells or of elicited cells such as polymorphonuclear neutrophils. There was no increase in the efficiency of infection after intervals of 2 or 7 days when induced macrophages would predominant. The reverse sequence of injections (scrapie-0.5 h-drug) had no effect despite the persistence of high scrapie titre in the peritoneum at the time of drug injection. However, the effect was restored by a second injection of scrapie in the sequence, scrapie-drug-scrapie. It is concluded that scrapie infection is established within minutes of injection but much of the inoculum is associated with peritoneal cells which are irrelevant to pathogenesis. Drugs may enhance the infection of relevant peritoneal cells or their targeting to the visceral lymphoreticular tissues where early replication takes place.
在腹腔注射羊瘙痒病病原体前2小时,给小鼠腹腔内单次注射16种不同药物。羊瘙痒病病原体以标准接种物的系列十倍稀释液进行注射,所获得的有效滴度用作衡量与注射生理盐水的小鼠相比,经处理小鼠的相对感染效率的指标。尽管所测试的药物种类繁多,但它们大多非特异性地使感染效率提高了0.6至2.1个对数10腹腔半数致死剂量单位(即4至126倍),但前提是药物和羊瘙痒病病原体均通过腹腔注射。间隔2小时或6小时时效果最佳,这表明可能涉及常驻腹膜细胞或诸如多形核中性粒细胞等募集细胞。在诱导巨噬细胞占主导的2天或7天间隔后,感染效率没有增加。尽管在注射药物时腹膜中羊瘙痒病病原体滴度仍然很高,但注射顺序相反(羊瘙痒病病原体-0.5小时-药物)却没有效果。然而,按照羊瘙痒病病原体-药物-羊瘙痒病病原体的顺序再次注射羊瘙痒病病原体后,效果得以恢复。结论是,羊瘙痒病感染在注射后几分钟内就已确立,但大部分接种物与对发病机制无关的腹膜细胞相关。药物可能会增强相关腹膜细胞的感染,或增强它们向早期发生复制的内脏淋巴网状组织的靶向性。