title: Metyrapone restores the febrile response to Escherichia coli LPS in pregnant rats.
abstract: Fever, an important component of the host's defense response to immune challenge, is absent or attenuated in rats near the term of pregnancy. The present experiments were carried out to determine the role of endogenous glucocorticoids in mediating the altered core temperature (Tc) response to exogenous pyrogen (i.e., Escherichia coli LPS). For the experiments, metyrapone-a glucocorticoid synthesis inhibitor-was administered to near-term pregnant rats prior to an EC(100) dose of E. coli LPS. Administration of LPS following vehicle elicited a significant corticosterone response and resulted in a decrease in Tc (i.e., hypothermia). Prior administration of metyrapone, however, which abolished the corticosterone response and altered the pyrogenic/cryogenic cytokine response to LPS, eliminated hypothermia and restored the febrile response. Our results provide evidence that endogenous glucocorticoids play a role in mediating the altered febrile response to immune stimuli observed in rats near the term of pregnancy.
authors.affiliation: Alberta Children’s Hospital Research Institute for Child and Maternal Health, Department of Physiology and Pharmacology, University of Calgary, Health Sciences Centre, Canada.
authors.forename: Brent N
authors.initials: BN
authors.lastname: Alexander
authors.forename: James E
authors.initials: JE
authors.lastname: Fewell
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000502:physiology; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology; D005938:Glucocorticoids / Q000378:metabolism; D007035:Hypothermia / Q000209:etiology* / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000009:adverse effects* / Q000378:metabolism; D008797:Metyrapone / Q000009:adverse effects* / Q000494:pharmacology; D023421:Models, Animal; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D003345:Corticosterone; D008797:Metyrapone