ABSTRACT
In the mid-1920s, Seibert (1) completed a series of classic studies, which proved conclusively that injection fevers associated with intravenous therapy resulted from heat-stable, filterable bacterial products that are commonly referred to as pyrogens. To ascertain the presence or absence of febrile responses caused by her test solutions, Seibert selected the rabbit as her animal test model, a choice that was later proven to be fortuitous (2). Since that time, many other species have been shown to have fever reactions when injected with bacterial pyrogens. Monkeys, horses, dogs, and cats, like the rabbit, have reproducible fever responses that are similar in nature to those of humans. On the other hand, the temperature response to pyrogens in rats, guinea pigs, mice, hamsters, and chicks is irregular and unpredictable, thus rendering them unsuitable for investigations of fever (3). For reasons of convenience and economics, the final selection of an animal test model for pyrogen testing was narrowed down to the dog and the rabbit. In 1942, Tui and Schrift (4), who had extensive experience with the two species, described the relative advantages and disadvantages of both. The rabbit has a labile thermoregulatory mechanism and frequently gives false-positive tests. For this reason, a negative test in a rabbit is more significant than a positive one. The dog, on the other hand, has a much more stable thermoregulatory mechanism, but is less sensitive to pyrogen than is the rabbit. A positive pyrogen response in a dog is so characteristic, with additional symptoms of leukopenia, vomiting, and diarrhea, that it is unmistakable. Therefore, a positive test for pyrogens in a dog is much more significant than a negative one. In summary, Tui and Schrift concluded that the rabbit was the better animal to use to test for the absence of pyrogens, but the dog was better used to establish the presence of pyrogens.
