Fever suppression in near-term pregnant rats is dissociated from LPS-activated signaling pathways
American Journal of Physiology. Regulatory Integrative and Comparative Physiology
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 g/kg ip). The
... 0 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-B (NF-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-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-1␤, IL-6, TNF-␣, and IFN-␥), 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 prostaglandinproducing enzyme called lipocalin-prostaglandin D 2 synthase in nearterm 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.