PGE2 produced in the periphery triggers the early phase of the febrile response to
infection and may contribute to later phases. It can be hypothesized that peripherally synthesized
PGE2 transmits febrigenic signals to the brain via vagal afferent nerves. Before testing this hypothesis, we investigated whether the febrigenic effect of intravenously administered
PGE2 is mediated by the brain and is not the result of a direct action of
PGE2 on thermoeffectors. In anesthetized rats, intravenously injected
PGE2 (100 microg/kg) caused an increase in sympathetic discharge to interscapular brown adipose tissue (iBAT), as well as increases in iBAT thermogenesis, end-expired CO2, and colonic temperature (Tc). All these effects were prevented by inhibition of neuronal function in the raphe region of the medulla oblongata using an intra-raphe microinjection of
muscimol. We then asked whether the brain-mediated
PGE2 fever requires vagal signaling and answered this question by conducting two independent studies in rats. In a study in anesthetized rats, acute bilateral cervical
vagotomy did not affect the effects of intravenously injected
PGE2 (100 microg/kg) on iBAT sympathetic discharge and Tc. In a study in conscious rats, administration of
PGE2 (280 microg/kg) via an indwelling jugular
catheter caused tail skin vasoconstriction, tended to increase oxygen consumption, and increased Tc; none of these responses was affected by total truncal subdiaphragmatic
vagotomy performed 2 wk before the experiment. We conclude that the febrile response to circulating
PGE2 is mediated by the brain, but that it does not require vagal afferent signaling.