Aa. Romanovsky et al., BIPHASIC FEVERS OFTEN CONSIST OF MORE THAN 2 PHASES, American journal of physiology. Regulatory, integrative and comparative physiology, 44(1), 1998, pp. 323-331
This paper disproves the common belief that all doses of lipopolysacch
aride (LPS) that are commonly referred to as biphasic fever inducing (
greater than or equal to 2 mu g/kg) cause truly biphasic responses. A
catheter was implanted into the right jugular vein of several strains
of adult male rats, and the animals were habituated to the experimenta
l conditions. At an ambient temperature of 30.0 degrees C, loosely res
trained animals were injected with a 10 mu g/kg dose of LPS (various p
reparations), and their colonic (T-c) and tail skin temperatures were
monitored (from greater than or equal to 1 h before to greater than or
equal to 7 h after the injection). The results are presented as time
graphs and phase-plane plots; in the latter case the rate of change of
T-c is plotted against T-c. In experiment 1 the intravenous injection
of LPS (from Escherichia coli 0111:B4, phenol extract) into the rats
(Bkl:Wistar) induced a triphasic febrile response, as is obvious from
time graphs of T-c (3 peaks), time graphs of effector activity (3 wave
s of tail skin vasoconstriction), and phase-plane plots (3 complete lo
ops); the injection of saline (control) induced no T-c changes. We ana
lyzed whether the triphasic pattern was due to some peculiarities of t
he experimental design, i.e., the pyrogen preparation used (experiment
2) or the rat strain tested (experiment 3) or whether this pattern re
flects a more general law. In experiment 2 we used the same (phenol) p
reparation of different LPS (from Shigella flexneri 1A and Salmonella
typhosa) and a different preparation (TCA extract) of the same LPS (E.
coli). Regardless of the LPS used, rats of the Bkl:Wistar strain resp
onded to the 10 mu g/kg dose with the triphasic fever. In experiment 3
, rats of other strains [Bkl: Sprague-Dawley and Sim:(LE)fBR(Black-hoo
ded)] were tested. Again, all animals responded to the 10 mu g/kg dose
off. coli LPS (phenol extract) with the triphasic fever. Because all
fevers caused by four different LPS preparations in three rat strains
were triphasic, the triphasic pattern is likely to constitute an intri
nsic characteristic of the febrile response.