Opposite effects of the synthetic adjuvant N-acetyl-muramyl-L-alanyl-D-isoglutamine on the immune response in mice depending on experimental conditions.

The influence of N-acetyl-muramyl-L-alanyl-D-isoglutamine (muramyl dipeptide, MDP) on the plaque-forming cell (PFC) response of mice to sheep red blood cells (SRBC) was studied. The effect of MDP depends on the relative doses of antigen and adjuvant and on the timing of adjuvant addition. For a given concentration of antigen, when SRBC and MDP were simultaneously injected in the i.v. route, MDP led to an enhancement of the response; in contrast, when antigen was injected i.p., a depression of the PFC response was observed. In vitro, the same duality of effect was obtained, for the same spleen cell concentration; addition of MDP led to a stimulation of the response when cultures were set in petri dishes and to an important decrease in the response when cultures were set up in plastic tubes. This inhibitory effect of MDP did not appear when it was added one night after the initiation of the cultures. These contrasting results confirm the adjuvant properties of MDP, but they show that under certain conditions, MDP can stimulate suppressive processes.