Prostacyclin-induced hyperthermia: implication of a protein mediator.

Intracerebroventricular administration of prostacyclin (PGI2) at room temperature (21 degrees C) induced dose-related hyperthermia in rabbits and also produced hyperthermia at low (4 degrees C) and high (30 degrees C) ambient temperatures. The PGI2-induced hyperthermia was not mediated by its stable metabolite 6-keto prostaglandin F1 alpha. Of the three anion transport systems (iodide, hippurate and liver-like) present in the choroid plexus, only the liver transport system seems to be important to central inactivation of pyrogen, prostaglandin E2 (PGE2) and the PGI2. Iodipamide (an inhibitor of the liver transport system) augmented the hyperthermia produced by PGI2, PGE2 and pyrogen. Phenoxybenzamine and pimozide had no thermolytic effect on PGI2-induced hyperthermia. After norepinephrine (NE) and dopamine levels were depleted by 6-hydroxydopamine, PGI2 still induced hyperthermia. Indomethacin and SC-19220 (a PG antagonist) did not antagonize PGI2-induced hyperthermia. Furthermore, the hyperthermia due to PGI2 was not accentuated by theophylline. In contrast, the hyperthermic response to PGI2 was attenuated by central administration of the protein synthesis inhibitor, anisomycin. These results indicate that PGI2-induced hyperthermia is not mediated by NE, dopamine, PGS, cyclic AMP, but, rather, that a protein mediator is implicated in the induction of fever by PGI2.