CONICET | Buscador de Institutos y Recursos Humanos

In addition to the central GABAergic receptors described for benzodiazepines, peripheral-type benzodiazepine receptor (PBR) were also identified for these molecules in immune cells, such as macrophages and lymphocytes. PBR activation was reported to decrease inflammatory immune responses. In this regard, we previously demonstrated that in an experimental autoimmune encephalomyelitis model (EAE) induced in rats, the diazepam (DZ) administration decreased the incidence and severity of clinical signs. However, how this drug diminishes the autoreactive inflammatory responses remains unclear. Moreover the dendritic cells (DC) are crucial to start specific immune responses, thus the DZ modulation of these cells could be critical to induce either inflammatory or regulatory responses. For this reason we studied the effect of DZ on the LPS induced DC maturation. DC derived from bone marrow of C57BL/6 mice were treated with several doses of DZ from 5 to 100 mM in the presence or absence of LPS. DZ did not induce changes in the viability of immature or mature DC at any dose, however co-treatment with LPS plus DZ (L/D) induced a reduction in the percentage of DC expressing MHCII and CD40 compared to LPS-DC. Besides, the simultaneous addition of DZ and LPS to DC culture inhibited the production of IL-12, IL-6 and TNF (p<0.05) induced by this TLR ligand. Besides, we treated DC with DZ in the presence or absence of LPS during 18 h, afterwards they were washed and co-cultured with allogeneic splenocytes. The L/D-DC were less capable to induce IL-17 and IFN-g production (p<0.05) in this allogeneic culture compared to LPS treated DC. Together these data suggest that DZ exerts suppressor mechanisms on DC activation which could be an interesting tool to modulate undesirable autoimmune responses as those occurring in multiple sclerosis.