Te. Scammell et al., VENTROMEDIAL PREOPTIC PROSTAGLANDIN-E2 ACTIVATES FEVER-PRODUCING AUTONOMIC PATHWAYS, The Journal of neuroscience, 16(19), 1996, pp. 6246-6254
Fever is thought to be initiated by pyrogenic cytokines inducing the p
roduction of prostaglandin E2 (PGE2) in the preoptic area (POA); PGE2
may act as a paracrine mediator that stimulates the neural pathways th
at raise body temperature. This essential role for prostaglandins in f
ever first was proposed 25 years ago, but the specific preoptic cell g
roups at which PGE2 acts and the pathways through which fever is produ
ced remain poorly understood. To better define the role of preoptic PG
E2 in fever, we developed a new method for combining acute brain injec
tions with Fos immunohistochemistry. We microinjected a threshold dose
of PGE2 to construct an anatomically detailed map of fever-producing
preoptic sites. The most pyrogenic preoptic sites were clustered along
the ventromedial aspect of the POA, surrounding and just anterior to
the organum vasculosum of the lamina terminalis. We then used Fos immu
nohistochemistry to identify the pattern of neural activation induced
by fever-producing preoptic injections of PGE2 and compared it with th
e Fos pattern seen after systemic immune stimulation. PGE2 fever was a
ccompanied by Fos induction in the ventromedial POA and the parvicellu
lar subnuclei of the paraventricular nucleus of the hypothalamus (PVH)
. In contrast to the Fos pattern seen after intravenous lipopolysaccha
ride administration, PGE2 injection did not induce Fos in the circumve
ntricular organs or the magnocellular subnuclei of the PVH. These obse
rvations establish a potential site of PGE2 action during fever and he
lp define candidate pathways through which fever occurs.