Effects of muramyl dipeptide and lead acetate on carbon clearance and endotoxin-induced mortality in mice.

Muramyl dipeptide (MDP) is a nonspecific immune adjuvant thought to affect the macrophage. MDP had been used safely without immunosuppressive or toxic side effects in our laboratory and others. Endotoxin, or lipopolysaccharide (LPS), is thought to be responsible for many of the systemic toxic effects of gram-negative infection. Lead acetate potentiates the lethal effects of endotoxin, an effect attributed to increased hepatotoxicity involving both hepatocytes and Kupffer macrophages. This study was undertaken to examine putative mechanism of action of MDP relating to the reticuloendothelial system. Endotoxin was given intraperitoneally to susceptible mice that were pretreated with MDP, lead acetate, or both, and to unmodified controls. Lead acetate significantly enhanced lethality due to LPS, but pretreatment with MDP did not alter mortality. Carbon clearance was measured in mice treated with MDP, lead, or both. There was no difference in the phagocytic index of control mice and those mice treated with lead acetate at various times prior to the injection. Carbon clearance increased significantly in mice pretreated with MDP but was unaltered by the addition of lead acetate. We conclude that if hyperphagocytosis of endotoxin occurs in MDP-pretreated mice, it does not cause additional mortality. Muramyl dipeptide appeared to be a safe reticuloendothelial stimulant that did not enhance the toxicity of lead or LPS in this experimental model.