11-12-epoxy-5-8-14-eicosatrienoic-acid and Fever

Inhibitors of cytochrome P-450 augment fever in rats and mice, indicating that the metabolite of the enzyme is candidate of endogenous antipyretic. Cytochrome P-450 of arachidonic acid cascade leads to the formation of regioisomeric 5,6-, 8,9- 11,12- and 14,15-epoxyeicosatrienoic acid (EET). Various isomers of EET were administrated into the preoptic area and anterior hypothalamus (PO/AH) to test their influence on fever induced by interleukin-1beta (IL-1beta) administrated into the PO/AH in conscious rats. The IL-beta-induced fever was attenuated in the 11,12-EET-pretreated rats, although 5,6-, 8,9- and 14,15-EET did not affect the fever. Intra-PO/AH injection of 11,12-EET did not alter normal body temperature. The results suggest that 11,12-EET acts in the hypothalamus as an endogenous antipyretic.

Topics: 8,11,14-Eicosatrienoic Acid; Analgesics, Non-Narcotic; Animals; Anterior Hypothalamic Nucleus; Arachidonic Acid; Cytochrome P-450 Enzyme System; Fever; Interleukin-1; Male; Preoptic Area; Rats; Rats, Wistar; Vasodilator Agents