Hypothalamic somatostatin may mediate endotoxin-induced fever in the rat

(1) The changes in rectal temperature produced by an injection of a bacterial endotoxin piromen (10-40 ng in 1.0 microliter) on somatostatin-14 (SS-14; 0.1-0.3 microgram in 1.0 microliter) into the preoptic anterior hypothalamic area were assessed and compared in control rats, in rats with hypothalamic SS depletion, and in rats with hypothalamic SS receptor blockade. (2) Intrahypothalamic injection of either piromen or SS-14 produced a dose-related rise in rectal temperature in intact, control rats. The fever induced by intrahypothalamic injection of piromen or SS-14, as well as that induced by intraperitoneal injection of piromen, was antagonized by pretreatment of the hypothalamus with a SS-14 receptor antagonist (0.1 ng in 1.0 microliter) in rats. (3) On the other hand, intraperitoneal administration of cysteamine (30-100 mg/kg), in addition to producing a dose-related fall in rectal temperature, also caused a dose-related fall in hypothalamic SS-levels in rats. Furthermore, the fever induced by intrahypothalamic injection of piromen, but not SS-14, was antagonized by depletion of hypothalamic SS levels with an intraperitoneal dose of cysteamine (30 mg/kg). (4) The results indicate that a somatostatinergic pathway in the hypothalamus may mediate endotoxin-induced fever in the rat.