Corticotropin-releasing factor attenuates interleukin 1-induced sleep and fever in rabbits

Interleukin 1 (IL-1), a key mediator of the acute phase response, stimulates hypothalamic corticotropin-releasing factor (CRF) release. The CRF-adrenocorticotrophic hormone (ACTH)-glucocorticoid axis is a feedback for peripheral production and action of IL-1. Effects of intracerebroventricularly administered CRF on rabbit sleepwake activity, brain temperature (Tbr), and behavior and on the central effects of IL-1 [fever and excess non-rapid-eye-movement sleep (NREMS)] were studied. CRF (0.1-1.25 micrograms) dose dependently decreased NREMS and enhanced wakefulness. IL-1-induced excess NREMS was inhibited by CRF. Rapid-eye-movement sleep (REMS) suppressed by IL-1 was partially restored by 0.1 or 0.5 microgram CRF, although CRF itself did not promote REMS. Behavioral effects of intracerebroventricular CRF were relatively small, although 1.25 micrograms abolished ingestion for 3 h, suppressed rearing behavior, and increased sitting behavior. Tbr increased after CRF injection alone. After IL-1 pretreatment, however, 0.1 and 0.5, but not 1.25, micrograms CRF reduced IL-1-induced fever after several hours. These results implicate IL-1-induced CRF release as part of a negative-feedback mechanism attenuating not only peripheral IL-1 actions but also its central effects.