Comparative studies between liposomes containing muramyl dipeptide and various immunomodulators on activation of mouse peritoneal macrophages and NK cells.

We compared the effects among muramyl dipeptide (MDP), liposome-encapsulated MDP (liposome MDP), bacillus Calmette-Guérin (BCG) and OK-432 on cytotoxic activity of mouse peritoneal macrophages (PM) and natural killer (NK) cells in vitro and in vivo, and their tumor-inhibitory effects against MH134 ascitic tumors in C3H/He mice. The cytotoxicity of PM induced by free MDP was lower than that induced by BCG, but a significantly higher cytotoxicity was induced by liposomes containing MDP and OK-432. The peritoneal NK cells were not activated by MDP, liposome MDP or BCG, but OK-432 profoundly augmented peritoneal NK activity. Growth inhibition of ascitic tumor was not observed in free MDP and BCG intraperitoneally treated mice, but moderate growth inhibition was noted in liposome-MDP-treated mice; and in OK-432-treated mice, marked tumor growth inhibition and prolongation of survival time were observed. These results suggested that OK-432 is more advantageous in controlling malignant tumor growth in vivo than free MDP, liposome MDP or BCG because of its ability to activate both macrophages and NK cells.