Inhibition of histamine release from dispersed canine skin mast cells by cyclosporin A, rolipram and salbutamol, but not by dexamethasone or sodium cromoglycate

Despite the important role that canine skin mast cells play in IgE-mediated allergic inflammation, clinically useful compounds for modulating mediator release from these cells or for suppressing cell response are lacking in the dog. The ability of five compounds to inhibit histamine release induced by non immunological (calcium ionophore A23187 and substance P) and IgE-dependent (concanavalin A) stimuli were compared. Sodium cromoglycate, a mast cell stabilizer, and dexamethasone, a glucocorticoid, failed to inhibit histamine release from isolated skin mast cells following any kind of stimulation. Salbutamol, a β-adrenergic agonist, exhibited inhibitory activity (46.0%) only after concanavalin A activation. In contrast, rolipram, a selective phosphodiesterase IV inhibitor and cyclosporin A, an immunosuppressor, showed potent anti allergic actions, inhibiting both IgE-dependent and -independent stimuli. Rolipram inhibited 42.8%, 44.7% and 19.2% of the mediator release induced by ionophore A23187, substance P and concanavalin A, respectively. Similarly cyclosporin A induced 85.9%, 14.9% and 67.3% inhibition after ionophore A23187, substance P and concanavalin A stimulation, respectively. These results suggest that rolipram and cyclosporin A merit to be clinically tested as agents for the treatment of chronic allergic diseases in the dog.