Anti-inflammatory effects of glucocorticoids and cyclosporin A on human basophils

Abstract

Pro-inflammatory and vasoactive mediators released from human basophils and mast cells play a role in several inflammatory and immune disorders. It was recently demonstrated that cyclosporin A (CsA) exerts anti-inflammatory effects by inhibiting the release of preformed and de novo synthesized mediators from human basophils. This study compared the effects of pharmacological concentrations of deflazacort (DFZ) and prednisolone (PRED) on the anti-IgE-mediated release of preformed (histamine) and de novo synthesized (leukotriene C4: [LTC4]) mediators from basophils. Basophils were cultured for 18 hours in the presence of pharmacological concentrations of DFZ (10(-8) to 3 x 10(-6) M). DFZ inhibited the anti-IgE-mediated release of histamine and LTC4 from basophils in a concentration-dependent manner (6-40%), and had a similar efficacy and potency to PRED. The effect of DFZ (10(-8) to 10(-7) M) in combination with CsA on the immunological release of histamine and LTC4 from basophils was also evaluated. An 18-hour incubation of basophils with DFZ (10(-8) M) followed by a short (15-minute) incubation with CsA (30 ng/ml) resulted in an additive inhibition of the release of histamine and LTC4. The additive anti-inflammatory effect of these drugs makes them interesting candidates for future controlled clinical trials in inflammatory diseases in which basophil-derived mediators play a relevant role.