Aa. Romanovsky et al., METHODOLOGY OF FEVER RESEARCH - WHY ARE POLYPHASIC FEVERS OFTEN THOUGHT TO BE BIPHASIC, American journal of physiology. Regulatory, integrative and comparative physiology, 44(1), 1998, pp. 332-338
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.