Loratadine and desethoxylcarbonyl‐loratadine inhibit the immunological release of mediators from human FcɛRI+cells

Summary Background Loratadine, a novel histamine H 1 ‐receptor antagonist, is effective in the treatment of patients with seasonal and perennial rhinitis and some allergic skin disorders. Histamine and other chemical mediators are synthesized and immunologically released by human peripheral blood basophils and tissue mast cells (FcɛRI + cells). Objective To evaluate the effects of loratadine and its main metabolite, desethoxylcarbonyl‐loratadine (des‐loratadine), on the immunological release of preformed (histamine and tryptase) and de novo synthesized mediators (leukotriene C 4 : LTC 4 and prostaglandin D 2 : PGD 2 ) from human FcɛRI + cells. Methods Human FcɛRI + cells purified from peripheral blood and from skin (HSMC) and lung tissue (HLMC) were preincubated with loratadine and des‐loratadine before immunological challenge with Der p 1 antigen or anti‐FcɛRI. The release of preformed mediators (histamine and tryptase) and de novo synthesized eicosanoids was evaluated in the supernatants of human FcRI + cells. Results Preincubation (15m in, 37°C) of purified (36–74%) basophils with loratadine (3 × 10 –6 –10 –4 M) and des‐loratadine before Der p 1 antigen or anti‐FcɛRI challenge concentration‐dependency (5–40%) inhibited the release of histamine and LTC 4 . Loratadine (3 × 10 –6 –l0 –4 M) and des‐loratadine also inhibited (10–40%) histamine, LTC 4 , and PGD 2 release from purified HLMC (16–68%) activated by anti‐FcɛRI. Loratadine (3 × 10 –6 –10 –4 M) and des‐loratadine caused concentration‐dependent inhibition (10–40%) of histamine, tryptase. LTC 4 , and PGD 2 release from purified HSMC (24– 72%) immunologically challenged with anti‐FcɛRI. Conclusion These results indicate that loratadine and its main metabolite have anti‐ inflammatory activity by inhibiting the release of preformed and de novo synthesized mediators from human FcɛRI + cells.