Repeated infusions of tnf[alpha] cause attenuation of the thermal
response and influence lps-fever in guinea pigs.
Goldbach, J[diaeresis]org-Michael, Joachim Roth, Birgit
St[diaeresis]orr, and Eugen Zeisberger.
Physiologisches Institut, Klinikum der Justus-Liebig
-Universit[umlaut]at, 35392 Giessen, Germany
APStracts 2:0310R, 1995.
Repeated infusions of TNF[alpha] cause attenuation of the thermal
response and influence LPS-fever in guinea pigs. Am. J. Physiol.
(Regulatory Integrative Comp. Physiol.) - In conscious, freely moving
guinea pigs tumor necrosis factors [alpha] und [beta] (TNF[alpha] and
TNF[beta]), infused into the aortic arch within 45 min at a dose of
5[mu]g/kg, induced different thermal responses. TNF[alpha] evoked a
biphasic elevation of abdominal temperature, both phases together
lasting longer than 6 h. In response to infusions of TNF[beta] the
first phase lasting about 120 min was the same as it was observed in
response to TNF[alpha], while the longer second phase of temperature
increase was missing. When the infusion of TNF[alpha] was repeated
four times in intervals of 3 days, the second phase of the increase
in abdominal temperature (120-360 min after start of infusion) tended
to decrease in response to the third and was significantly attenuated
in response to the fourth infusion of TNF[alpha]. A control group of
guinea pigs received 4 infusions of solvent (0.9 % sterile pyrogen
-free saline). Another 3 days after the fourth infusion of TNF[alpha]
or solvent all animals were injected with 20 [mu]g/kg bacterial
lipopolysaccharide (LPS from Escherichia coli, intramuscular
injection). In those guinea pigs having developed a reduced
responsiveness to TNF[alpha], the first phase of LPS-induced fever
was significantly suppressed while the second phase tended to be
enhanced, compared to animals having received 4 infusions of solvent.
In conclusion, a reduced responsiveness to TNF[alpha] develops in
guinea pigs after its repeated administration. In the state of lower
reactivity to exogenous TNF[alpha], a reduced response of the first
phase of LPS-induced fever (during which endogenous TNF[alpha] is
released) can be observed. This indicates that endogenous TNF[alpha]
may contribute to LPS-induced fever only in the initial phase of the
febrile response of guinea pigs.
Received 1 August 1995; accepted in final form 18 October 1995.
APS Manuscript Number R484-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 30 November 95