METHODOLOGY OF FEVER RESEARCH - WHY ARE POLYPHASIC FEVERS OFTEN THOUGHT TO BE BIPHASIC

This study explains why the recently described triphasic lipopolysacch aride (LPS) fevers have been repeatedly mistaken for biphasic fevers. Experiments were performed in loosely restrained male Wistar rats with a catheter implanted into the right jugular vein. Each animal was inj ected with Escherichia coli LPS, and its colonic (T-c) and tail skin t emperatures were monitored. The results are presented as time graphs a nd phase-plane plots; in the latter case the rate of change of T-c is plotted against T-c. At an ambient temperature (T-a) of 30.0 degrees C , the response to the 10 mu g/kg dose of LPS was triphasic, as is obvi ous from time graphs of T-c (3 peaks), time graphs of effector activit y (3 waves of tail skin vasoconstriction), and phase-plane plots (3 co mplete loops). When the T-a was below neutral (22.0 degrees C) or the LPS dose was higher (100 or 1,000 mu g/kg), the time graph of T-c did not allow for the reliable detection of all three febrile phases, but the phase-plane plot and time graph of effector activity clearly revea led the triphasic pattern. In a separate experiment, LPS (10 mu g/kg) or saline was injected via one of two different procedures: in the fir st group the injection was performed through the jugular catheter, fro m outside the experimental chamber; in the second group the same nonst ressing injection was combined with opening the chamber and pricking t he animal in its lower abdomen with a needle. In the first group the f ebrile response was obviously triphasic, and none of the phases was du e to the procedure of injection per se (injection of saline did not af fect T-c). In the second group the fever similarly consisted of three T-c rises, but it might have been readily mistaken for biphasic becaus e the first rise was indistinguishable from stress hyperthermia occurr ing in the saline-injected (and needle-pricked) controls. We conclude that several methodological factors (dose of LPS, procedure of its inj ection, and T-a) have contributed, although each in a different way, t o the common misbelief that there are only two febrile phases.