Diazepam inhibits acute innate and ongoing adaptive inflammatory responses

C R FALCON; MONFERRAN C; . CERVI L.; ROTH G

Mar del Plata

Congreso; LXII Reunión anual. Sociedad Argentina de Inmunología; 2014

Sociedad Argentina de Inmunología

663. (721) DIAZEPAM INHIBITS ACUTE INNATE AND ONGOING ADAPTIVE INFLAMMATORY RESPONSES Falcón, Cristian Roberto1; Monferrán Clara G. 1; Cervi Laura2; Roth Germán A. 1. Centro de Investigaciones en Química Biológica de Córdoba1- Centro de Investigaciones en Bioquímica Clínica e Inmunología (CIBICI)-CONICET-UNC2 In addition to the central GABAergic receptors described for benzodiazepines, peripheral-type benzodiazepine receptor (PBR) was also identifid for these molecules in immune cells, such as macrophages and lymphocytes. PBR activation was reported to decrease inflmmatory immune responses. In this regard, we previously demonstrated that Diazepam (Dz) decreases LPS-induced dendritic cell activation and their ability to induce allogeneic responses, thus preventing the initiation of immune responses. In this work we demonstrate that Dz is able to diminish acute innate and adaptive ongoing inflmmatory responses in vivo. For this, we treated C57BL/6 mice with Dz (2mg/Kg) at days 0, 2 and 4, and 12 h after the last treatment the mice were injected (i.p.) with 800 µg de LPS. Dz was able to prevent LPS-induced death and inhibit the IL-6 secretion (p<0,001) by peritoneal cells favoring IL-10 production (p<0.002). On the other hand, mice with MOGinduced experimental autoimmune encephalomyelitis (EAE) were treated (i.p.) with Dz (2mg/Kg) on alternate days starting when the clinical score 1 was reached. The treatment dramatically decreased EAE progression evidenced by visible clinical signs which did not increase from the beginning of the injections. Moreover, Dz treatment impaired MOG-specifi IL-17 (p<0.03) and IFN-β (p<0,001) production by cells of draining lymphatic nodes. Together these data suggest that Dz is able to suppress both, innate and adaptive dependent inflmmatory responses, which could be an interesting tool to modulate undesirable immune responses as those occurring in septic shock or multip