Activation of human monocytes by free muramyl dipeptide (MDP).

Activation of human monocytes with MDP (N-acetylmuramyl-L-alanyl-D-isoglutamine) 1-100 micrograms per ml for 48 h in vitro enhanced the cytostatic activity against the target cell line K-562, while cytolysis remained unchanged. Catalase, 600 SU per ml, had no inhibitory effect on the cytostasis mediated by MDP-activated monocytes. The optimal MDP concentration for activation was in the range 3-10 micrograms per ml. Supernatants from monocytes activated with MDP 1-30 micrograms per ml for 48 h exerted no cytostatic activity. MDP 1-100 micrograms per ml had no direct cytostatic or cytolytic effect on the target cells in a 24 h assay. When added to monocytes cultured in vitro for four days immediately prior to the chemiluminescence (CL)-assay, MDP 10-100 micrograms per ml enhanced both the zymosan and phorbol myristate acetate-triggered lucigenin-dependent CL. Monocytes pre-activated with MDP for 48 h did not demonstrate any enhanced CL-response. MDP-activation 30 micrograms per ml for 48 h increased the zymosan-triggered generation of H2O2 moderately. The enhanced cytostatic activity induced by MDP-activation is probably not mediated by hydrogen peroxidase or production of cytostatic factors.