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

Abstract

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 μg/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 bothin vivo andin 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).