The first and second phases of biphasic fever {symbol 190 \f "
symbol"} two sequential stages of the sickness syndrome?.
Romanovsky, Andrej A., Vladimir A. Kulchitsky, Nikolai V. Akulich,
Stanislaw V. Koulchitsky, Christopher T. Simons, Daniel I. Sessler,
and Valery N. Gourine.
Thermoregulation Laboratory, Legacy Research, Legacy Portland
Hospitals, Portland, Oregon 97227; Institute of Physiology,
Belarusian Academy of Sciences, Minsk 220625, Belarus;
Thermoregulation Research Laboratory, Department of Anesthesia,
University of California at San Francisco, San Francisco, California
94143
APStracts 3:0061R, 1996.
We hypothesized that the systemic inflammatory response undergoes two
consecutive stages, each characterized by different nonspecific
sickness patterns. To test this hypothesis, we studied thermal,
nociceptive, and motor responses to lipopolysaccharide (LPS) in 43
unanesthetized, habituated, and lightly restrained male Wistar rats
previously implanted with a catheter into the jugular vein. E. coli
LPS was injected i.v. in a dose of 0, 0.1, 1, 10, 100, or 1000
{SYMBOL 109 \f "Symbol"}g/kg. Colonic temperature (Tc) was
measured with a thermocouple. Changes in nociception were assessed by
the tail flick latency (TFL) to a noxious heat stimulus. Motor
activity was evaluated using an observation-based activity score
(AS). The two lowest doses were apyrogenic. The next dose induced a
monophasic fever with a maximal Tc rise of 0.9 {SYMBOL 177 \f
"Symbol"} 0.2{SYMBOL 176 \f "Symbol"}C at 108 {SYMBOL
177 \f "Symbol"} 11 min post-LPS. The next two higher doses
caused biphasic fevers with the first and second peaks of 0.7 {SYMBOL
177 \f "Symbol"} 0.1 and 1.4 {SYMBOL 177 \f "Symbol"}
0.1{SYMBOL 176 \f "Symbol"}C (10 {SYMBOL 109 \f
"Symbol"}g/kg) and 0.7 {SYMBOL 177 \f "Symbol"} 0.1
and 1.4 {SYMBOL 177 \f "Symbol"} 0.2{SYMBOL 176 \f
"Symbol"}C (100 {SYMBOL 109 \f "Symbol"}g/kg)
occurring at 60 {SYMBOL 177 \f "Symbol"} 6 min and 165
{SYMBOL 177 \f "Symbol"} 17 min and at 45 {SYMBOL 177 \f
"Symbol"} 3 and 141 {SYMBOL 177 \f "Symbol"} 6 min,
respectively. The highest dose of LPS resulted in a Tc fall (nadir,
-0.6 {SYMBOL 177 \f "Symbol"} 0.1{SYMBOL 176 \f
"Symbol"}C at 83 {SYMBOL 177 \f "Symbol"} 6 min). Two
different sickness patterns were exhibited. The first {SYMBOL 190 \f
"Symbol"} high Tc, low TFL, and high AS {SYMBOL 190 \f
"Symbol"} occurred during the monophasic fever and the first
(early) phase of the biphasic fevers; it was termed "the early
phase syndrome." The second pattern {SYMBOL 190 \f
"Symbol"} high or low Tc, high TFL, and low AS {SYMBOL 190 \f
"Symbol"} developed during the second (late) phase of the
biphasic fevers and LPS-hypothermia (endotoxin shock); it was termed
"the late phase syndrome." Occurring at different stages of
the systemic inflammatory response and developing through different
coping patterns (fight/flight {SYMBOL 190 \f "Symbol"} energy
expenditure vs. depression/withdrawal {SYMBOL 190 \f
"Symbol"} energy conservation), the two syndromes represent
two different types of adaptation to infection and have different
biological significance. Viewing sickness as a dynamic entity is
justified clinically. Such a dynamic approach to the problem resolves
several contradictions in the current concept of sickness.
Received 11 October 1995; accepted in final form 14 February
1996.
APS Manuscript Number R640-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 March 96