THE INHIBITORY EFFECT OF DIAZEPAM ON INDUCED LPS-DENDRITIC CELL ACTIVATION

FALCÓN CRISTIAN; FERNANDEZ HURST NICOLAS; CERVI LAURA; MONFERRÁN CLARA G; ROTH GERMÁN A.

Los Cocos

Congreso; LXI Reunion anual de la Sociedad Argentina de Inmunologia; 2013

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