Romanovsky, Andrej A., and Yelena K. Karman. Posthemorrhagic antipyresis: what stage of fever genesis is affected? J. Appl. Physiol. 83(2): 359-365, 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 (T_re) responses to LPS from Salmonella typhi (200 ng/kg iv), ethanol-purified preparation of homologous IL-1 (1 ml from 3.5 × 10⁷ cells, 1.5 ml/kg iv), and PGE₂ (1 µg, intracisternal injection). The effect of hemorrhage on T_re 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 T_re rise of 0.4 ± 0.1 instead of 1.2 ± 0.2°C at the time of the second peak), the monophasic T_re response to IL-1 (by ~0.5°C for over 1-5 h postinjection), and the PGE₂-induced hyperthermia (0.4 ± 0.1 vs. 0.9 ± 0.1°C, maxima). In afebrile animals, the hemorrhage neither affected T_re at thermoneutrality nor changed the T_re 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.