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Am J Physiol Regul Integr Comp Physiol 283: R1346-R1353, 2002. First published August 29, 2002; doi:10.1152/ajpregu.00396.2002
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Vol. 283, Issue 6, R1346-R1353, December 2002

Attenuated fever in pregnant rats is associated with blunted syntheses of brain cyclooxygenase-2 and PGE2

Kyoko Imai-Matsumura1, Kiyoshi Matsumura2, Akira Terao3, and Yasuyoshi Watanabe4

1 Department of Life and Health Sciences, Hyogo University of Teacher Education, Hyogo 673-1494; 2 Department of Intelligence Science and Technology, Graduate School of Informatics, Kyoto University, Kyoto 606-8501; 4 Department of Physiology, Osaka City University Graduate School of Medicine, Osaka 545-8585, Japan; and 3 Molecular Neurobiology Laboratory, SRI International, Menlo Park, California 94025

Attenuation of fever occurs in pregnant animals. This study examined a hypothesis that brain production of PGE2, the final mediator of fever, is suppressed in pregnant animals. Near-term pregnant rats and age-matched nonpregnant female rats were injected with lipopolysaccharide (100 µg/kg) intraperitoneally. Four hours later, colonic temperature was measured, their cerebrospinal fluid (CSF) was sampled for PGE2 assay, and their brains were processed for immunohistochemistry of cyclooxygenase-2, an enzyme involved in PGE2 biosynthesis. In the pregnant rats, lipopolysaccharide injection resulted in significantly smaller elevations in both colonic temperature and CSF-PGE2 level than in nonpregnant rats. In the pregnant rats, lipopolysaccharide-induced cyclooxygenase-2 expression was blunted in terms of the number of positive cells. There was a significant correlation between PGE2 level in CSF and the number of cyclooxygenase-2-positive endothelial cells. These results suggest that suppressed PGE2 production in the brain is one cause for the attenuated fever response at near-term pregnancy and that this suppressed PGE2 production is due to the suppressed induction of cyclooxygenase-2 in brain endothelial cells.

prostaglandin; endothelial cell; lipopolysaccharide; cytokine


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