Effects of muramyl dipeptide on sleep, body temperature and plasma copper after intracerebral ventricular administration

Abstract

Muramyl peptides are the monomeric components of bacterial cell wall peptidoglycans. Many muramyl peptides, such as muramyl dipeptide (MDP), (N-acetylmuramyl- l-alanyl- d-isoglutamine) , are immune response modifiers, pyrogenic and somnogenic. The purposes of this study were to measure the somnogenic effects of MDP in conjunction with a biochemical measure of the host defense response, plasma Cu, and to determine if plasma Cu levels, like sleep, are regulated by a central nervous system process. MDP administered into a lateral cerebral ventricle induced a dose-dependent rise in plasma copper at 28 h postinfusion. This was usually associated with dose-dependent fevers, increases in SWS and reductions in rapid eye movement (REM) sleep during the first 6 h after infusion. Intravenous (i.v.) administration of the same amount of MDP did not affect any of these variables. We conclude that the syndrome induced by centrally administered MDP includes activation of the host defense response with respect to a rise in plasma copper in addition to fever and enhanced sleep.