Failure of synthetic muramyl dipeptide to increase antibacterial resistance

Abstract

Synthetic muranyl dipeptide, which potentiates antibody production and cellular immune responses at a dosage of 100 to 500 micrograms, did not enhance resistance to intravenous infection with a sublethal dose of 2 X 10(3) to 4 X 10(3) viable Listeria monocytogenes cells in mice when intraperitoneally injected either 20 min or 5 days before infection. Similarly, blockade of the mononuclear phagocyte system by dextran sulfate 500 could not be overcome by pretreatment with muramyl dipeptide. In contrast, dextran sulfate 500-induced loss of antibacterial resistance was found to be completely abolished by intraperitoneal injection of 3 X 10(9) killed Bordetella pertussis organisms when given 4 days before injection of dextran sulfate 500, i.e., 5 days before infection. B. pertussis were also effective in enhancing antibacterial resistance when administered 5 days before infection. The different behavior of the two adjuvants tested is assumed to be due to their different nonspecific proliferative capacities. Thus, B. pertussis are assumed to act by direct stimulation of the mononuclear phagocyte system whereas muramyl dipeptide does not.