Endotoxin fever in the new-born guinea-pig and the modulating effects of indomethacin and p-chlorophenylalanine

Abstract

1. At 30 degrees C ambient temperature E. coli endotoxin injected into the cerebral ventricles evokes a febrile response in 0-3 day-old guinea-pigs. If the dose is sufficiently high, the fever is biphasic: two rising phases separated by a transient fall.2. At 20 degrees C ambient temperature the change in body temperature after the endotoxin is still biphasic, but the transient fall is more pronounced and, finally, hypothermia develops. The relatively large surface area of the new-born cannot explain, by itself, the hypothermia.3. The phasic changes in body temperature following endotoxin administration are unlikely to be mediated by a single central factor, and a sequence of several factors could be postulated.4. Indomethacin prevents the first-phase febrile rise in body temperature, and also the consequent fall, but not the second-phase rise.5. p-Chlorophenylalanine pre-treatment prevents the transient fall only, it slightly increases the first-phase rise and does not influence the second-phase rise.6. Prostaglandins and/or other derivatives of endogenous arachidonic acid in the brain might be responsible for the first rising phase of the endotoxin fever, and might also initiate a central serotonergic mechanism which, in turn, could lead to the transient falling phase between the two rising phases of fever. The mechanism of the second-phase febrile rise in body temperature awaits some other explanation.