Rapid elimination of a synthetic adjuvant peptide from the circulation after systemic administration and absence of detectable natural muramyl peptides in normal serum at current analytical limits

Although it is clear that muramyl peptides are involved in sleep associated with bacterial infection, their role in normal physiological sleep is less certain. It has been speculated that "natural" muramyl peptides, derived from degraded gut flora, may pass into the bloodstream, where they play a role in normal sleep (M. Karnovsky, Fed. Proc. 45:2556-2560, 1986). Muramic acid serves as a chemical marker for muramyl peptides, since it is not synthesized by mammals. After injection of synthetic muramyl dipeptide in rabbits, muramic acid was readily detected (after release by acid hydrolysis) in the circulation; however, levels rapidly decreased. This was an important positive control in assessing circulating levels of natural muramyl peptides. Muramic acid was not found in normal serum (detection limit, approximately 500 pmol/ml), demonstrating the absence of appreciable amounts of circulating natural muramyl peptides. At this time we are unable to provide supportive evidence for Karnovsky's hypothesis.