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

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 [1]. 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 × 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^-8 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.