Suppressive effect of diazepam on IFN-gamma production by human T cells

Many studies showed that benzodiazepines could modulate immune responses through interaction with peripheral benzodiazepine receptors (PBRs) in immune cells but most of the studies were focused on monocytes and macrophages. In the present study, we revealed that diazepam, a mixed-type benzodiazepine, inhibited IFN-gamma production by human peripheral blood mononuclear cells (PBMCs) induced by anti-CD3 in dose-dependent manner. Flow cytometry analysis demonstrated that diazepam could inhibit the frequency of IFN-gamma-producing CD4(+) and CD8(+) T cells. The inhibitory effect of diazepam on IFN-gamma production is similar to that of R(0)5-4864, a selective PBRs ligand. However, D8555, a selective ligand for PBRs in microglia in the central nervous system, is a much weak inhibitor compared with R(0)5-4864 or diazepam. The inhibitory effect of R(0)5-4864 could be antagonized by PK11195, which is recognized as selective PBRs antagonist, and suppressive effect of diazepam on T cells is partially antagonized by PK11195. Collectively, these results suggested that diazepam suppressed human T cell function through PBRs.