Mifepristone (RU38486) influences the core temperature response of term pregnant rats to intraperitoneal lipopolysaccharide.
Pregnancy alters the cytokine, prostanoid and core temperature responses of rats to infectious stimuli at a time when blood levels of the endogenous glucocorticoid corticosterone are elevated. Given that glucocorticoids attenuate bacterial pyrogen-induced fever in rats, the present experiments were carried out to test the hypothesis that administration of RU38486, a glucocorticoid type II receptor antagonist, would restore the febrile response to E. coli lipopolysaccharide (LPS) in pregnant rats on day 21 of gestation. Pregnant rats were randomly allocated to one of four experimental groups depending upon whether they received RU38486 (20 mg kg(-1) intragastric) or vehicle followed by E. coli LPS (160 microg kg(-1)i.p.; a minimal dose that elicits maximal febrile response in non-pregnant rats) or vehicle. Basal core temperature was not altered by intragastric administration of RU38486 or vehicle. Following intragastric administration of vehicle, intraperitoneal administration of E. coli LPS produced a significant hypothermia with latency, duration and magnitude of 0.5 h, 2 h and -1.3 degrees C, respectively. Following intragastric administration of RU38486, however, intraperitoneal administration of E. coli LPS elicited only a minimal decrease in core temperature which was not significantly different from control values. Thus, our data provide evidence that endogenous glucocorticoids play a role in modulating the early core temperature response to a relatively large dose of bacterial pyrogen in rats at term of pregnancy.
Moore
Sherry L
SL
Department of Physiology & Biophysics, University of Calgary, Calgary, Alberta T2N 4 N1, Canada.
Fewell
James E
JE
D000818:Animals; D001831:Body Temperature / Q000187:drug effects / Q000276:immunology*; D001833:Body Temperature Regulation / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000276:immunology* / Q000517:prevention & control*; D005938:Glucocorticoids / Q000276:immunology*; D007155:Immunologic Factors / Q000276:immunology; D007274:Injections, Intraperitoneal; D008070:Lipopolysaccharides; D015735:Mifepristone / Q000008:administration & dosage*; D011247:Pregnancy; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*
D005938:Glucocorticoids; D007155:Immunologic Factors; D008070:Lipopolysaccharides; D011965:Receptors, Glucocorticoid; D015735:Mifepristone