Benzodiazepines are also widely used substances. They are used as sedative, anxiolytic, anticonvulsive, and muscle relaxing drugs. They act as modulators of the gamma-amino-butyric-acid (GABA) receptors in the central nervous system (CNS) which are the most important inhibitory receptors in the CNS [12]. GABA receptors consist of several subunits, not all of them interacting with benzodiazepines. Sedative effects of benzodiazepines are mediated by α1-subunits and anxiolytic and anticonvulsant effects by the α2- and α3-subunits [13]. The classical benzodiazepines like diazepam (ValiumR) show all of the typical effects; more recently introduced substances are more selective GABA receptor agonists in order to reduce side effects such as memory impairment and abuse potential [14].

In addition to the receptors in the CNS, there exist also peripheral benzodiazepine receptors. Also known as 18 kDa translocator protein (TSPO) they are multimeric complexes of 18 kDa proteins found in most peripheral organs in high density. They are localized in the outer mitochondrial and have been associated with increased steroid synthesis and transport of cholesterol to the inner mitochondrial membrane and with increases in cell proliferation such as cancer and gliosis, but also tissue repair and immunomodulating functions [15]. In the CNS, they are mainly expressed by activated microglial cells and are considered to play a role also in neuroinflammatory processes [16]. TSPO ligands have been shown in experimental models to have anti-inflammatory effects [17, 18].

The data about benzodiazepines leading to immune suppression are not many. Old reports postulated that peripheral benzodiazepine receptors may be involved in the development of immune cells in neonatal rats [19] and diazepam and methamphetamine have been found to suppress the antibody production and T-cell function in mice [20]. In animal models we found that diazepam had a profound negative effect on the resistance of mice against poxvirus infection as well as the development of a virus specific antibody response. Additionally the proliferative response of human lymphocytes/spleen cells was also inhibited by benzodiazepines [21]. Evidence for a direct immunomodulatory action for benzodiazepines emerged also from studies that demonstrated the presence of TSPO on immune/inflammatory cells and diazepam effects were discussed as being related to the number of TSPO sites present on immune cells [22].