Intraperitoneal infection with scrapie is established within minutes of injection and is non-specifically enhanced by a variety of different drugs

Abstract

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 predominate. 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. © 1990 Springer-Verlag.