Attenuation of fever at near term: is interleukin-6-STAT3 signalling altered?
Pregnant rats in late gestation show a reduced fever response after stimulation with lipopolysaccharide (LPS). This can result from either an increased action of endogenous antipyretics or a reduction in the production or action of endogenous pyrogens. Nonpregnant rats given LPS release interleukin (IL)-6, which causes nuclear translocation of the signal transducer and activator of transcription 3 (STAT3) in the vascular organ of the lamina terminalis (OVLT), followed by a significant increase in core body temperature. The present study investigated whether the reduced fever response in near-term pregnant rats is associated with a reduced nuclear STAT3 response. Rats at gestation day 15 (G15), gestation day 21 (G21, near term) and at lactation day 5 (L5) were injected with LPS (50 microg/kg, i.p.) or vehicle. Only near-term pregnant rats responded with an attenuated body temperature during the fever response. Immunohistological analysis indicated no significant difference in nuclear STAT3 in the OVLT of the different animal groups 2 h after LPS. Measurement of total and phosphorylated STAT3 protein in the OVLT with semiquantitative western blot revealed no significant differences of this protein among these immune challenged animal groups. IL-6 concentrations were also similar at G15, G21 and L5 2 h after injection of LPS. These results lead to the conclusion that the attenuation of the fever response at near-term pregnancy is not associated with a reduced amount of nuclear STAT3 in the OVLT, indicating a maintained IL-6-STAT3 signalling pathway in the OVLT.
Harré
E-M
EM
Hotchkiss Brain Institute, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada. harre@ucalgary.ca
Mouihate
A
A
Pittman
Q J
QJ
D000818:Animals; D001831:Body Temperature; D001833:Body Temperature Regulation / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D005334:Fever / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood*; D008070:Lipopolysaccharides / Q000276:immunology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D018709:Statistics, Nonparametric; D013495:Supraoptic Nucleus / Q000378:metabolism*
D015850:Interleukin-6; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat