Differential effects of benzodiazepines on immune responses in non-stressed and stressed animals

Benzodiazepines (BZDs) used extensively as antianxiety agents are known for their low toxicity. However, a long lasting depression of mitogen stimulated secretion of macrophage-derived cytokines has been shown in offsprings of rats that were exposed to diazepam during pregnancy. The Present study investigates the effects of long term administration of diazepam and alprazolam on humoral and cell-mediated immune responses in adult male Wistar rats and Swiss albino mice. Administration of diazepam (5 mg/kg/day x 7-14 d) and alprazolam (1 mg/kg/day x 7-14 d) produced a significant reduction of anti-SRBC antibody titre, a measure of humoral immune response, and foot pad thickness and % leucocyte migration inhibition (% LMI), measures of cell-mediated immune responses. Administration of diazepam (5 mg/kg, i.p.) or alprazolam (1 mg/kg, i.p.) before subjecting the animals to restraint stress (RS) reversed the immunosuppressive effects of RS. Both per se immunosuppressive effects and attenuation of RS-induced immunosuppression of BZDs was antagonized by flumazenil (10 mg/kg, i.p.), a central BZD receptor antagonist. Thus, BZDs appear to modulate the immune system in non-stressed and stressed adult animals in a differential manner and these effects are mediated via central benzodiazepine receptors.