Two muramyl
dipeptides,
N-acetylmuramyl-L-alanyl-D-isoglutamine and its adjuvant-inactive isomer N-acetylmuramyl-D-alanyl-D-
isoglutamine, were examined for their ability to protect mice carrying the CBA/N immune deficiency gene (xid) against lethal bacterial challenge. Prophylactic treatment with
N-acetylmuramyl-L-alanyl-d-isoglutamine gave significant protection against Streptococcus pneumoniae, Salmonella typhimurium, and Salmonella enteritidis
infection. N-Acetylmuramyl-D-alanyl-D-
isoglutamine was unable to confer protection. Incorporation of the lipophilic
glycerol dipalmitate derivatives of the two muramyl
dipeptides within liposomal carriers resulted in a significant enhancement of anti-infectious activity, both with respect to number of survivors and length of survival. Liposomal muramyl
dipeptides were 10- to 15-fold more potent than free
muramyl dipeptide; enhanced potency was most evident with N-acetylmuramyl-D-alanyl-D-
isoglutamine. Prophylactic treatment with
liposomes containing the lipophilic muramyl
dipeptides resulted in enhanced clearance of bacteria from the blood (greater than 3-fold increase in rate) when compared with that of hydrosoluble
N-acetylmuramyl-L-alanyl-D-isoglutamine, indicating a correlation between reticuloendothelial stimulation and anti-infectious activity.