Prevention of experimental septic shock by pretreatment of mice with muramyl peptides.

Muramyl peptides, immunostimulators with macrophage as a main target cell, are used for protecting mice from LPS-lethality (the experimental model of septic shock). Different protocols of pretreatment mice by muramyl peptides lead to opposite results. LPS and glycopeptides act synergistically in the induction of lethal shock, when mice receive peptides 1 day prior to lethal dose of LPS. However, extension of the period between the peptide and LPS injections to 6 days cancels the effect of synergism. Moreover, a 14-day interval between the same injections leads to protection of 70-90% animals from the toxic effect of LPS. Lipophilic analogs require 10-100 lower concentrations to protect the animals than the parent highly hydrophilic glycopeptides. Production of TNF, IL-1 and phagocytosis by macrophages was studied within the periods corresponding to "synergism" and LPS-resistance. High level of macrophage activity was observed during the "synergism" period. Low TNF production and reduced macrophage phagocyte activity corresponded to LPS-resistant state. These results partly explain the LPS-unresponsiveness in mice after their pretreatment by muramyl peptides.