Muramyl peptide enhancement of slow-wave sleep

Sleep-promoting Factor S, derived from brain or urine, has been characterized as a muramyl peptide. In rabbits, one pmol of Factor S induced excess slow-wave sleep (SWS) for several hours following cerebral intraventricular infusion. Factor S also induced increases in EEG slow-wave (1/2-4 Hz) amplitudes similar to those observed during the deep sleep that follows sleep deprivation. Sleep following Factor S treatment remained normal in that it was episodic and waking behaviours such as eating, drinking and grooming persisted. The structure of Factor S is similar to those of naturally occurring monomers of bacterial cell wall peptidoglycans. Other muramyl peptides such as muramyl dipeptide (MDP) were also found to be somnogenic. Structure-activity studies of various MDP derivatives indicated that somnogenic activity is dependent on precise structural requirements. Muramyl peptides also are immunomodulators and pyrogens. These activities could be separated from somnogenic activity by using various MDP derivatives or by pharmacologic intervention. Muramyl peptides may induce their somnogenic effects through the release of the cytokine interleukin-1; interleukin-1 also has the capacity to induce excess SWS. Although muramyl peptides have many biological activities in mammals, the role(s) they may play in mammalian physiology remains unknown. It is possible that mammalian tissue may store and/or modify muramyl peptides in conjunction with their use as modulators of sleep, temperature and immune responses.