Augmentation of immune responses by a muramyl dipeptide analog, MDP-Lys(L18)

The effects of N2-(N-acetyl-muramyl-L-alanyl-D-isoglutamyl)-N6-stearoyl-L-lysine (MDP-Lys(L18], a muramyl dipeptide (MDP) analog, on the immune responses in mice were studied. MDP-Lys(L18) augmented the mitogenic responses of splenic lymphocytes to phytohemagglutinin (PHA) and lipopolysaccharide (LPS) at 0.1-10 micrograms/ml, and antibody formation to sheep red blood cell (SRBC) in normal and immunosuppressed mice, and to dinitrophenyl (DNP)-Ficoll. In addition, MDP-Lys(L18) potentiated polyclonal B cell activation both in vivo and in vitro. It was also found that MDP-Lys(L18) augmented the cellular immune responses, such as mixed lymphocyte reaction (MLR) and delayed type hypersensitivity (DTH). These effects of MDP-Lys(L18) were more potent than those of MDP. These findings may be attributed to the interleukin 1 (IL-1)-inducing activity of MDP-Lys(L18).