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.