Prevention of experimental endotoxin shock by a monocyte activator.

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.