Fever suppression in near-term pregnant rats is dissociated from LPS-activated signaling pathways

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2005-11, Vol.58 (5), p.R1265-R1272
• Main Authors: MOUIHATE, A, ELLIS, S, HARRE, E.-M, PITTMAN, Q. J
• Format: Article
• Language: English
• Subjects: Animal bacterial diseases; Bacterial diseases; Biological and medical sciences; Brain; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Cytokines; Fever; Fundamental and applied biological sciences. Psychology; Infectious diseases; Medical sciences; Pregnancy; Rodents; Signal transduction; Vertebrates: nervous system and sense organs
• ISSN: 0363-6119; 1522-1490

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 micro g/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-[kappa]B (NF-[kappa]B), 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-[kappa]B 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, TNFalpha-, 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.[PUBLICATION ABSTRACT]