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Volume 16, Number 19,
Issue of October 1, 1996
pp. 6246-6254
Copyright ©1996 Society for Neuroscience
Ventromedial Preoptic Prostaglandin E2 Activates
Fever-Producing Autonomic Pathways
Received May 30, 1996; revised July 10, 1996; accepted July 15, 1996.
Thomas E. Scammell,
Joel K. Elmquist,
John D. Griffin, and
Clifford B. Saper
Department of Neurology and Program in Neuroscience, Beth Israel
Hospital and Harvard Medical School, Boston, Massachusetts 02215
Fever is thought to be initiated by pyrogenic cytokines inducing
the production of prostaglandin E2 (PGE2) in the preoptic area (POA);
PGE2 may act as a paracrine mediator that stimulates the neural
pathways that raise body temperature. This essential role for
prostaglandins in fever first was proposed 25 years ago, but the
specific preoptic cell groups at which PGE2 acts and the pathways
through which fever is produced remain poorly understood. To better
define the role of preoptic PGE2 in fever, we developed a new method
for combining acute brain injections 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 immunohistochemistry to identify the
pattern of neural activation induced by fever-producing preoptic
injections of PGE2 and compared it with the Fos pattern seen after
systemic immune stimulation. PGE2 fever was accompanied by Fos
induction in the ventromedial POA and the parvicellular subnuclei of
the paraventricular nucleus of the hypothalamus (PVH). In contrast to
the Fos pattern seen after intravenous lipopolysaccharide
administration, PGE2 injection did not induce Fos in the
circumventricular organs or the magnocellular subnuclei of the PVH.
These observations establish a potential site of PGE2 action during
fever and help define candidate pathways through which fever
occurs.
Key words:
fever;
prostaglandin E2;
body temperature;
thermoregulation;
autonomic system;
Fos;
preoptic area;
hypothalamus
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