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Thermoregulation Laboratory, Legacy Holladay Park Medical Center, Portland, Oregon 97208-3950
This paper disproves the common belief that
all doses of lipopolysaccharide (LPS) that are commonly referred to as
biphasic fever inducing (
2 µg/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 experimental conditions. At an ambient temperature of 30.0°C, loosely restrained animals were injected with a 10 µg/kg dose of LPS (various
preparations), and their colonic
(Tc) and tail skin temperatures
were monitored (from 1 h before 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
Tc is plotted against
Tc. 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
Tc (3 peaks), time graphs of
effector activity (3 waves of tail skin vasoconstriction), and
phase-plane plots (3 complete loops); the injection of saline (control)
induced no Tc changes. We analyzed
whether the triphasic pattern was due to some peculiarities of the
experimental design, i.e., the pyrogen preparation used
(experiment 2) or the rat strain tested (experiment 3) or whether
this pattern reflects a more general law. In
experiment 2 we used the same (phenol)
preparation 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 responded to the 10 µg/kg dose with the triphasic fever. In experiment 3, rats of other strains [Bkl:Sprague-Dawley and
Sim:(LE)fBR(Black-hooded)] were tested. Again, all animals
responded to the 10 µg/kg dose of E. 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 intrinsic characteristic of the febrile response.
febrile response; skin vasoconstriction; lipopolysaccharide preparations; rat strains; body temperature oscillations; nonlinear dynamics; phase plane
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