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 I day prior to letha l 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 i nterval between the same injections leads to protection of 70-90% animals f rom the toxic effect of LPS. Lipophilic analogs require 10-100 lower concen trations to protect the animals than the parent highly hydrophilic glycopep tides. Production of TNF, IL-1 and phagocytosis by macrophages was studied within the periods corresponding to "synergism" and LPS-resistance. High le vel of macrophage activity was observed during the "synergism" period. Low TNF production and reduced macrophage phagocyte activity corresponded to LP S-resistant state. These results partly explain the LPS-unresponsiveness in mice after their pretreatment by muramyl peptides. (C) 2001 Elsevier Scien ce BN. All rights reserved.