Fever suppression in near-term pregnant rats is dissociated from LPS-activated signaling pathways.
Near-term pregnant rats show a suppressed fever response to LPS that is associated with reduced induction of cyclooxygenase (COX)-2 in the hypothalamus. The objective of this study is to explore whether the LPS-activated signaling pathways in the fever-controlling region of the hypothalamus are specifically altered at near term. Three rat groups consisting of 15-day pregnant rats, near-term 21- to 22-day pregnant rats, and day 5 lactating rats were injected with a febrile dose of LPS (50 mug/kg ip). The hypothalamic preoptic area and the organum vasculosum of the lamina terminalis (OVLT) were collected 2 h after LPS injection. The activation of three transcription modulators, nuclear factor-kappaB (NF-kappaB), extracellular signal-regulated kinase 1/2 (ERK1/2), and signal transducer and activator of transcription 5 (STAT5), was assessed using semiquantitative Western blot analysis. LPS activated the NF-kappaB pathway in all rat groups, and this response was not altered at near term. ERK1/2 and STAT5 were constitutively activated during all reproductive stages, and their levels were not significantly affected by LPS injection. Plasma levels of the proinflammatory cytokines (IL-1beta, IL-6, TNF-alpha, and IFN-gamma), anti-inflammatory cytokines (IL-4, IL-10, and IL-1 receptor antagonist), and corticosterone were unaffected during the three reproductive stages after LPS challenge. We observed a sharp decrease in the expression of a prostaglandin-producing enzyme called lipocalin-prostaglandin D2 synthase in near-term pregnant and lactating rats. Thus fever suppression at near term is not due to an alteration in either LPS-activated intracellular signaling pathways or LPS-induced pro- and anti-inflammatory cytokine production.
Mouihate
A
A
Hotchkiss Brain Institute, Dept. of Physiology and Biophysics, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada. mouihate@ucalgary.ca
Ellis
S
S
Harré
E-M
EM
Pittman
Q J
QJ
D000818:Animals; D003345:Corticosterone / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D004789:Enzyme Activation; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D048370:MAP Kinase Kinase 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011247:Pregnancy; D015230:Prostaglandin D2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; D015230:Prostaglandin D2; D003345:Corticosterone