Here we report for the first time that
MCS-18, a novel
natural product isolated from Helleborus purpurascens, is able to inhibit the expression of typical molecules of mature dendritic cells (DC) such as CD80, CD86, and especially of CD83 subsequently leading to a clear and dose-dependent inhibition of the DC-mediated T-cell stimulation. Furthermore,
MCS-18 impeded the formation of the typical DC/T-cell clusters, which are essential to induce potent immune responses. Interestingly,
MCS-18 also inhibited CCR7 expression on DC which subsequently lead to a dose-dependent block of the CCL19-mediated DC migration.
MCS-18 not only inhibited the DC-mediated T-cell stimulation but also the anti-CD3/anti-CD28-mediated T-cell stimulation. Strikingly,
MCS-18 also strongly reduced the
paralysis associated with the
experimental autoimmune encephalomyelitis (EAE), which is a murine model for human
multiple sclerosis, in a prophylactic as well as in a "real" therapeutic setting. Even when the EAE was induced for a second time, the MCS-18-treated animals were still protected, suggesting that
MCS-18 induces a long-lasting suppressive effect. In addition, and very important for the potential practical application in humans,
MCS-18 was also active when administered orally.
MCS-18 treatment almost completely reduced leukocyte infiltration in the brain and in the spinal cord. In conclusion, using in vitro as well in vivo assays we were able to show that
MCS-18 exerts a strong immunosuppressive activity with remarkable potential for the
therapy of diseases characterized by a pathologically over-activated immune system.