Anti-infectious activity of liposomal muramyl dipeptides in immunodeficient CBA/N mice.
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.
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000818:Animals; D001424:Bacterial Infections / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects; D007153:Immunologic Deficiency Syndromes / Q000276:immunology*; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA / Q000276:immunology*; D008811:Mice, Inbred DBA / Q000276:immunology; D011008:Pneumococcal Infections / Q000276:immunology; D012481:Salmonella Infections, Animal / Q000276:immunology; D012477:Salmonella enteritidis / Q000276:immunology; D012486:Salmonella typhimurium / Q000276:immunology
D000119:Acetylmuramyl-Alanyl-Isoglutamine