Attenuated fever in pregnant rats is associated with blunted syntheses of brain cyclooxygenase-2 and PGE2.
Attenuation of fever occurs in pregnant animals. This study examined a hypothesis that brain production of PGE(2), 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 microg/kg) intraperitoneally. Four hours later, colonic temperature was measured, their cerebrospinal fluid (CSF) was sampled for PGE(2) assay, and their brains were processed for immunohistochemistry of cyclooxygenase-2, an enzyme involved in PGE(2) biosynthesis. In the pregnant rats, lipopolysaccharide injection resulted in significantly smaller elevations in both colonic temperature and CSF-PGE(2) 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 PGE(2) level in CSF and the number of cyclooxygenase-2-positive endothelial cells. These results suggest that suppressed PGE(2) production in the brain is one cause for the attenuated fever response at near-term pregnancy and that this suppressed PGE(2) production is due to the suppressed induction of cyclooxygenase-2 in brain endothelial cells.
Imai-Matsumura
Kyoko
K
Department of Life and Health Sciences, Hyogo University of Teacher Education, Hyogo 673-1494.
Matsumura
Kiyoshi
K
Terao
Akira
A
Watanabe
Yasuyoshi
Y
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000503:physiopathology*; D007527:Isoenzymes / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D008070:Lipopolysaccharides / Q000494:pharmacology; D016015:Logistic Models; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000134:cerebrospinal fluid; D051381:Rats; D017208:Rats, Wistar
D007527:Isoenzymes; D008070:Lipopolysaccharides; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone