Hyperthermic effects of arachidonic acid, prostaglandin E2 and F2alpha in rats.

The aim of the present study was to investigate the possibility that endotoxin fever in rats is mediated by arachidonic acid (AA) which in turn is converted to the active metabolites such as prostaglandin (PG) E2, PGF2alpha, thromboxane A2 (TxA2), or prostacyclin (PGI2). Evidence is presented indicating that PGE2 induces fever (not hyperthermia) by acting on the anterior hypothalamic preoptic area. Conversely, both PGF2alpha and AA produce mutually similar hyperthermia and there is no correlation between their microinjection sites in the diencephalon and the observed hyperthermic response. In addition, evidence is presented suggesting that involvement of other metabolites of AA, namely TxA2 and PGI2 in the mediation of endotoxin fever in rats seems unlikely. Only PGE2-induced fever is significantly similar, consistent with the parameters of this study, to endotoxin-induced fever in rats. AA-induced hyperthermia is probably brought about by increased levels of PGF2alpha or both PGF2alpha and PGE2 in the hypothalamus following AA injection. It seems highly unlikely that endotoxin produces fever in rats through the increased availability of free AA or through the activation of the PG endoperoxide synthetase in the hypothalamus. The mechanism by which endotoxin may increase PGF2 levels in the rat hypothalamus remains unknown.

Mediation of hyperthermia by prostaglandin E2: a new hypothesis.

In rat hypothalamus prostaglandin (PG) E2, unlike PGF2 or arachidonic acid shared the site of hyperthermic action with E. coli endotoxin. The in vitro catabolism of PGE2 in the hypothalami of endotoxin-treated rats was significantly suppressed. It is proposed that endotoxin fever in rats is due to the inhibition of PGE2 breakdown in the hypothalamus.