Fever and survival in the rat. The effect of enhancing fever

To study the effect of fever on infectious disease in a mammal, rats, partially restrained by an antirotatory device and with chronically implanted preoptic thermodes, were injected with Salmonella enteritidis and, in some of them, the hypothalamus was then continuously cooled to enhance the febrile response. All animals developed a fever that peaked 2 days after the infection, reaching 40.9 +/- 0.2 (SD) degrees C in the nine hypothalamic cooled and only 39.8 +/- 0.4 degrees C in the 13 control animals (P less than 0.001). All the hypothalamic cooled animals died within 8 days of infection, whereas only 23% of the controls had died after 28 days of infection (P = 0.0006). When the hypothalamus was continuously cooled in five uninfected animals, rectal temperature increased to 40.9 +/- 0.3 degrees C but 24 h later it had decreased to 39.6 +/- 0.3 (P less than 0.025). This decrease in body temperature suggests that the hypothalamic thermosensors had partially lost their effectiveness. It is concluded that cooling the hypothalamus increases the mortality rate in rats infected with S. enteritidis and that this effect could be mediated by the high body temperature or by the concomitant metabolic and endocrine responses thus induced.