Differences in interleukin 1 (IL-1), IL-6, tumor necrosis factor and IL-1 receptor antagonist production by human monocytes stimulated with muramyl dipeptide (MDP) and its stearoyl derivative, romurtide.

The immunostimulatory reagents muramyl dipeptide (MDP) and its stearoyl derivative romurtide [MDP-Lys(L18)] were assessed for cytokine inducing activity in human monocytes. Both MDP and romurtide stimulated the production of interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF) and IL-1 receptor antagonist (IL-1Ra). Kinetics study indicated that IL-1, TNF and IL-1Ra were induced after 4 h stimulation but IL-6 was produced at a later phase. Romurtide induced these cytokines for longer period that MDP. Dose-response study indicated that romurtide was far more potent than MDP in induction of IL-1, IL-6 and TNF. Although the magnitude of the IL-1 and IL-6 induction was almost the same, that of TNF induction was greater in romurtide-stimulated monocytes than in MDP-stimulated cells. Among IL-1, IL-1 beta appeared to be a major product. In contrast to other cytokines, IL-1Ra was induced by MDP and romurtide in a similar dose and time dependent manner with similar magnitude of response. These studies indicate that MDP and romurtide, especially romurtide, are very potent inducers of both immunostimulatory and immunosuppressive cytokines by human monocytes but with different efficacy and kinetics.