Pyrogens Enhance b-Endorphin Release in Hypothalamus and Trigger Fever That Can Be Attenuated by Buprenorphine

At first, we investigated whether both b-endorphin release level in the hypothalamus and body temperature can be altered after intracerebroventricular (i.c.v.) injection of either lipopolysaccharide (LPS), interleukin-1b (IL-1b), or prostaglandin E sub(2) (PGE sub(2)) in rats. It was found that in the rat, i.c.v. administration of either LPS (0.5 kg in 10 kl), IL-1b (10 ng in 10 kl), or PGE sub(2) (200 ng in 10 kl), in addition to producing fever, upregulated the immunoreactivity of b-endorphin in the preoptic anterior hypothalamus of rat brain. Secondarily, we assessed whether the fever induced by either LPS, IL-1b, or PGE sub(2) can be altered by pretreatment with buprenorphine (an opioid receptor antagonist). The results revealed that i.c.v. administration of buprenorphine (1 - 10 kg in 10 kl) alone had an insignificant effect on the body temperature. However, the fever induced by i.c.v. injection of either LPS, IL-1b, or PGE sub(2) was significantly attenuated by pretreatment with i.c.v. injection of buprenorphine 1 h before the pyrogen injection in rats. The results suggest that pyrogens enhance b-endorphin release in the hypothalamus and trigger fever which can be attenuated by buprenorphine, an opioid receptor antagonist.