Prevention of experimental endotoxin shock by a monocyte activator.

Abstract

In patients with polytrauma or major surgery, severe bacterial infections leading to septic shock and multiorgan failure are still a major cause of death. Prevention of septic shock in patients at risk would be an alternative to treatment of patients with overt septic shock. We therefore conducted a trial with the monocyte activator muramyl tripeptide phosphatidylethanolamine (MTP-PE) in an experimental pig model. Liposome encapsulated MTP-PE (50 micrograms/kg of body weight) or liposomes alone were given intravenously at 72 or 24 h before endotoxemia was induced by lipopolysaccharide (LPS), simultaneously with the induction of endotoxin shock, or 1 h thereafter. Pretreatment with MTP-PE at 72 and 24 h before endotoxemia was induced resulted in a reduction of endotoxin shock-induced mortality from 81.8% (9 of 11 animals) in the control group to 8.3% (1 of 12 animals) of the MTP-PE-pretreated animals (P < 0.001). The administration of MTP-PE 24 h before the induction of endotoxin shock was more effective (P < 0.01) than administration of MTP-PE 72 h before endotoxemia was induced (P = 0.05). The pretreated animals did not develop fever or cardiovascular complications, and pulmonary function was significantly improved. Furthermore, the alpha-form of the soluble CD14 LPS receptor in pig serum showed a marked decrease in LPS-treated animals, and this decrease was reduced by MTP-PE pretreatment at 24 h before endotoxemia was induced. When MTP-PE was given simultaneously with the induction of septic shock or 1 h thereafter, it did not influence either mortality or morbidity. In conclusion, pretreatment of pigs with MTP-PE improves several parameters of endotoxin shock and it reduces mortality. Patients with high risk of developing septic complications might benefit from a pretreatment with this monocyte-activating substance.

• Authors: B Passlick, M O Labeta, J R Izbicki, P Ostertag, T Löffler, M Siebeck, U Pichlmeier, L Schweiberer, H W Ziegler-Heitbrock
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 39 Issue 11 Pg. 2535-40 (Nov 1995) ISSN: 0066-4804 [Print] United States
• PMID: 8585740 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunologic Factors
• Lipopolysaccharide Receptors
• Lipopolysaccharides
• Liposomes
• Phosphatidylethanolamines
• mifamurtide
• Acetylmuramyl-Alanyl-Isoglutamine

Topics

• Acetylmuramyl-Alanyl-Isoglutamine (administration & dosage, analogs & derivatives, therapeutic use)
• Animals
• Blood Pressure (drug effects)
• Brucella abortus
• Fever (prevention & control)
• Heart Rate (drug effects)
• Immunologic Factors (administration & dosage, therapeutic use)
• Leukocyte Count (drug effects)
• Lipopolysaccharide Receptors (immunology)
• Lipopolysaccharides (blood, toxicity)
• Liposomes
• Macrophage Activation (drug effects)
• Monocytes (drug effects)
• Phosphatidylethanolamines (administration & dosage, therapeutic use)
• Salmonella
• Shock, Septic (complications, physiopathology, prevention & control)
• Swine