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Anti-infectious activity of liposomal muramyl dipeptides in immunodeficient CBA/N mice.

Abstract
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.
AuthorsN C Phillips, L Chedid
JournalInfection and immunity (Infect Immun) Vol. 55 Issue 6 Pg. 1426-30 (Jun 1987) ISSN: 0019-9567 [Print] United States
PMID3553001 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Acetylmuramyl-Alanyl-Isoglutamine
Topics
  • Acetylmuramyl-Alanyl-Isoglutamine (pharmacology)
  • Animals
  • Bacterial Infections (immunology)
  • Immunity, Innate (drug effects)
  • Immunologic Deficiency Syndromes (immunology)
  • Male
  • Mice
  • Mice, Inbred CBA (immunology)
  • Mice, Inbred DBA (immunology)
  • Pneumococcal Infections (immunology)
  • Salmonella Infections, Animal (immunology)
  • Salmonella enteritidis (immunology)
  • Salmonella typhimurium (immunology)

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