In vivo treatment with benzodiazepines inhibits murine phagocyte oxidative metabolism and production of interleukin 1, tumor necrosis factor and interleukin-6

Abstract

We reported previously that benzodiazepines, widely prescribed for their anxiolytic properties, bind to specific receptors on macrophages and modulate in vitro their metabolic oxidative responsiveness. This study was designed to investigate the in vivo effects of benzodiazepine molecules on several macrophage functions. Benzodiazepines injected i.p. exerted a long-lasting inhibition on phagocyte oxidative responsiveness, still detectable 48 hr after injection. This action was dose-dependent, optimally effective at 1 mg/kg and observed at the site of injection within peritoneal cells as well as at a distance, within splenocytes. It was restricted to peripheral and mixed-type molecules whereas the central-type compound, clonazepam, was ineffective, in good keeping with the molecular specificity of the receptor present on murine macrophages. The fact that benzodiazepines exerted similar effects in Nude mice highly suggests that their in vivo inhibitory activity was not T cell-dependent. The peripheral benzodiazepine Ro5-4864 injected i.p. inhibited the capacity of macrophages to produce interleukin-1, tumor necrosis factor and interleukin-6. Clonazepam remained ineffective. These results demonstrate an in vivo immunosuppressive property of peripheral and mixed but not central -type benzodiazepines affecting characteristic phagocyte functions involved in host-defense mechanisms as well as in inflammatory response.