Beneficial effect of liposome-encapsulated muramyl tripeptide in experimental septicemia in a porcine model.
In a porcine model of pneumococcal septicemia, animals were pretreated with 1 mg of liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (MTP-PE) or with liposomes alone. After 24 h each animal received an injection of either 10(9) or 10(10) pneumococcal serotype 6B cells. MTP-PE pretreatment resulted in less pronounced leukocytopenia, with a nadir of 6,700 (versus 4,100) leukocytes per mm3 after injection of 10(9) bacteria and a nadir of 4,400 (versus 3,800) leukocytes per mm3 after injection of 10(10) bacteria. At the same time bacterial clearance was substantially improved by MTP-PE pretreatment. Finally, pretreatment with MTP-PE dramatically reduced mortality; the average death rates for both series of animals used were 55% for liposome-pretreated animals and 3% for animals pretreated with MTP-PE-containing liposomes. These results in a preclinical model suggest that treatment with MTP-PE-containing liposomes might be beneficial in controlling septicemia in patients at risk.
Izbicki
J R
JR
Department of Surgery, University of Munich, Federal Republic of Germany.
Raedler
C
C
Anke
A
A
Brunner
P
P
Siebeck
M
M
Leinisch
E
E
Lüttiken
R
R
Ruckdeschel
G
G
Wilker
D K
DK
Schweiberer
L
L
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007958:Leukocyte Count; D008081:Liposomes / Q000008:administration & dosage; D009000:Monocytes / Q000276:immunology; D011008:Pneumococcal Infections / Q000188:drug therapy; D018805:Sepsis / Q000188:drug therapy* / Q000401:mortality; D013534:Survival; D013552:Swine; D013556:Swine, Miniature
D008081:Liposomes; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C035104:muramylNAc-Ala-isoGln-Lys-tripeptide