Modulation of nonspecific antimicrobial resistance of mice to Klebsiella pneumoniae septicemia by liposome-encapsulated muramyl tripeptide phosphatidylethanolamine and interferon-gamma alone or combined.
Activation of the host defense system in a nonspecific way might provide tools to support failing antibiotic treatment in certain infectious diseases. The antimicrobial effect was investigated of liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (MTPPE) and interferon (IFN)-gamma and liposome-coencapsulated MTPPE and IFN-gamma on Klebsiella pneumoniae septicemia in mice. Prophylactic treatment of mice with five doses of liposomal MTPPE or IFN-gamma increased survival from 0 to 65%. Administration of MTPPE and IFN-gamma coencapsulated in liposome resulted in 100% survival. In vitro, peritoneal macrophages by themselves were stimulated by these agents but were unable to kill K. pneumoniae. However, production of both oxygen and nitrogen intermediates increased when immunomodulators were added to macrophages. These results indicate that effective prophylactic treatment of septicemia due to K. pneumoniae with coencapsulated MTPPE and IFN-gamma is not solely due to activation of the resident macrophages.
ten Hagen
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TL
Department of Clinical Microbiology and Antimicrobial Therapy, Erasmus University, Rotterdam, Netherlands.
van Vianen
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W
Bakker-Woudenberg
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IA
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000276:Adjuvants, Immunologic; D000818:Animals; D016470:Bacteremia / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D002478:Cells, Cultured; D004337:Drug Carriers; D004338:Drug Combinations; D004339:Drug Compounding; D004347:Drug Interactions; D005260:Female; D005609:Free Radicals; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use*; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D007711:Klebsiella pneumoniae / Q000276:immunology*; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010714:Phosphatidylethanolamines / Q000008:administration & dosage / Q000627:therapeutic use*; D013047:Specific Pathogen-Free Organisms; D016019:Survival Analysis
D000276:Adjuvants, Immunologic; D004337:Drug Carriers; D004338:Drug Combinations; D005609:Free Radicals; D008081:Liposomes; D010714:Phosphatidylethanolamines; C037144:mifamurtide; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D007371:Interferon-gamma