A sleep-promoting factor was extracted from human urine. Intraventricular infusion of the purified material induced excess slow-wave sleep in rats and rabbits for 5--10 h after the infusion. Chemical properties of the urinary factor were similar to those of factor S derived from whole brains of sleep-deprived goats, sheep, and rabbits. The behavior of the urinary factor in two ion exchange chromatographic steps, high voltage electrophoresis, gel-filtration, and ultrafiltration was similar to that of factor S. Effects of the purified urinary factor on slow-wave sleep of rats and rabbits were similar in time-course and duration to those of factor S from brain. However, the factor obtained from human urine did not increase the amplitude of cortical slow waves to the same extent as did factor S from brains of sleep-deprived animals.
Inflammatory cytokines may affect cerebral circulation under pathological conditions. Responses of cerebral pial arterioles to one such cytokine, interleukin (IL)-1 beta and its inhibitor [soluble IL-1 receptor (sIL-1R)] were examined in anesthetized newborn pigs using closed cranial windows. Levels of prostanoids and cyclic nucleotides in periarachnoid cerebral spinal fluid (CSF) were measured. To examine the structure-activity relationship of the parent IL-1 beta molecule, two IL-1 beta fragments with amino acid sequences of 187-204 [IL-1 beta-(187-204)] and 208-240 [IL-1 beta-(208-240)] were tested for their effects on pial arterioles. Diameter changes of pial arterioles were sequentially recorded every 5 min for 30 min after topical application of IL-1 peptides. CSF was sampled at the end of the 30 min. IL-1 beta dose dependently induced arteriolar dilation and increased prostaglandin E2 (PGE2), 6-keto-PGF1 alpha adenosine 3',5'-cyclic monophosphate (cAMP), and guanosine 3',5'-cyclic monophosphate (cGMP). Intravenous indomethacin blocked the IL-1 beta-induced vasodilation, the increased prostanoids, and the increased cAMP, but not the increased cGMP. Neither heat-inactivated IL-1 beta nor IL-1 beta vehicle affected arteriolar diameter or CSF levels of prostanoids. The sIL-1R blocked the IL-1 beta-induced vasodilation and the increased CSF prostanoids. IL-1 beta-(208-240) also induced pial arteriolar dilation; however, its vasodilatory potency was 1,000 times less than that of the whole IL-1 beta molecule. IL-1 beta-(187-204) did not induce pial arteriolar dilation even when its dose was increased to the level of IL-1 beta-(208-240). These results suggest that IL-1 beta, through the activation of membrane-bound IL-1 beta receptors, induces pial arteriolar dilation via mechanisms that involve prostanoids and cyclic nucleotides. The results also indicate that the 208-240 amino acid sequence of IL-1 beta has a sequence-specific physiological function.
The effects of human interleukin 1 (IL 1) on the architecture of rabbit sleep-wake cycles and brain temperature (Tbr) changes coupled to states of vigilance were examined. Cerebral intraventricular infusion of IL 1 induced increased slow-wave sleep (SWS), increased electroencephalographic slow-wave (0.5-4 Hz) amplitudes, and fever. Heat-inactivated IL 1 failed to elicit these responses. IL 1 also significantly inhibited rapid-eye-movement (REM) sleep; however, inactivated IL 1 also reduced REM sleep; thus some of the IL 1-induced REM reduction may be related to the infusion process. The duration and number of sleep cycles (REM-to-REM interval) were unaffected by IL 1. Similarly, Tbr changes that normally occur during the transition from one arousal state to another remained unchanged after IL 1 infusion, even though rabbits were simultaneously febrile. We conclude that IL 1 selectively enhances SWS while leaving sleep cycles and Tbr changes coupled to states of vigilance undisturbed.
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