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.
Opp
M
M
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163.
Obál
F
F
Krueger
J M
JM
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000502:physiology; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D005334:Fever / Q000139:chemically induced* / Q000503:physiopathology; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D011817:Rabbits; D012890:Sleep / Q000187:drug effects*; D012894:Sleep Stages / Q000187:drug effects
D007375:Interleukin-1; D003346:Corticotropin-Releasing Hormone