Posthemorrhagic antipyresis: what stage of fever genesis is affected?. Romanovsky, Andrej A., and Yelena K. Karman. Thermoregulation Laboratory, Legacy Research, Legacy Portland Hospitals, Portland, Oregon 97227; and Institute of Physiology, Belarusian Academy of Sciences, Minsk 220725, Belarus
APStracts 4:0143A, 1997.
It has been shown that hemorrhage leads to a decreased thermal responsiveness to lipopolysaccharide (LPS). The aim of this study was to clarify what stage of fever genesis [production of endogenous pyrogens such as interleukin 1 (IL 1), increase of the prostaglandin E2 (PGE2) concentration in brain tissue, activation of cold-defense effectors] is deficient in posthemorrhagic antipyresis. In adult rabbits, we evaluated the effect of acute hemorrhage (15 ml/kg) on the rectal temperature (Tr) responses to LPS from Salmonella typhi (200 ng/kg, i.v.), ethanol-purified preparation of homologous IL 1 (1 ml from 3.5 107 cells, 1.5 ml/kg, i.v.), and PGE2 (1 (g, intracisternal injection). The effect of hemorrhage on Tr was also studied in afebrile rabbits, both at thermoneutrality (23(C) and during ramp cooling (to 7(C). The hemorrhage strongly attenuated the biphasic LPS-induced fever (a Tr rise of 0.4 ( 0.1 instead 1.2 ( 0.2( at the time of the second peak), the monophasic Tr response to IL 1 (by ca. 0.5(C for over 1-5 h postinjection), and the PGE2 hyperthermia (0.4 ( 0.1 vs. 0.9 ( 0.1(C, maxima). In afebrile animals, the hemorrhage neither affected Tr at thermoneutrality nor changed the Tr response to cold exposure. The data suggest that neither "insufficiency" of cold-defense effectors nor lack of endogenous mediators of fever (IL 1, PGE2) can be the only or even the major cause of posthemorrhagic antipyresis. We speculate that fever genesis is altered at a stage occurring after the intrabrain PGE2 level is increased but before thermoeffectors are activated. 

Received 27 January 1997; accepted in final form 28 March 1997.
APS Manuscript Number A84-7.
Article publication pending Journal of Applied Physiology.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 15 April 1997