PYROGENICITY OF ETIOCHOLANOLONE AND INTERLEUKIN-1 IN NEW AND OLD-WORLD MONKEYS

Etiocholanolone (5 beta-androstan-3 alpha-ol-17-one; designated E) is one of the major products of metabolism of testosterone and androstene dione (androst-4-ene-3,17-dione) in many mammalian species, including humans. E and several other 5 beta-reduced steroids have been found to induce fever in humans. The pyrogenic effect of these steroids has be en shown to be due to the release of interleukin-1 (IL-1) from the leu kocytes that are mobilized in response to the steroid injections. Old World Monkeys such as Rhesus monkeys (Macaca mulatta), metabolize andr ogens similarly to humans, and E is a normal metabolite. However, New World Monkeys such as Squirrel monkeys (Saimiri sciureus), lack hepati c 5 alpha- and 5 beta-steroid reductases and excrete androgens primari ly in an unaltered state; E is not produced. Therefore, we postulate t hat Squirrel monkeys likewise may have lost the ability to respond to 17-ketosteroids such as E. To test this hypothesis, adult male Rhesus and Squirrel monkeys were treated with E, and their rectal temperature s were recorded over a 24-hr period. Rhesus monkeys exhibited a rise o f up to 3 degrees F following E injection, Squirrel monkeys, on the ot her hand, did not exhibit any increase in rectal temperature over the 24-hr period, even when doses up to 250 times the effective human dose were used. However, both species responded to injected IL-1 alpha wit h a robust increase in rectal temperature. The data show that E is pyr ogenic in Rhesus, but not Squirrel monkeys. The findings support the n otion that injected E may induce release of IL-1 in Rhesus monkeys, bu t not in Squirrel monkeys.