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

Summary BackgroundLoratadine, a novel histamine H1‐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). ObjectiveTo evaluate the effects of loratadine and its main metabolite, desethoxylcarbonyl‐loratadine (des‐loratadine), on the immunological release of preformed (histamine and tryptase) andde novosynthesized mediators (leukotriene C4: LTC4and prostaglandin D2: PGD2) from human FcɛRI+cells. MethodsHuman 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) andde novosynthesized eicosanoids was evaluated in the supernatants of human FcRI+cells. ResultsPreincubation (15m in, 37°C) of purified (36–74%) basophils with loratadine (3 × 10–6–10–4M) and des‐loratadine before Der p 1 antigen or anti‐FcɛRI challenge concentration‐dependency (5–40%) inhibited the release of histamine and LTC4. Loratadine (3 × 10–6–l0–4M) and des‐loratadine also inhibited (10–40%) histamine, LTC4, and PGD2release from purified HLMC (16–68%) activated by anti‐FcɛRI. Loratadine (3 × 10–6–10–4M) and des‐loratadine caused concentration‐dependent inhibition (10–40%) of histamine, tryptase. LTC4, and PGD2release from purified HSMC (24– 72%) immunologically challenged with anti‐FcɛRI. ConclusionThese results indicate that loratadine and its main metabolite have anti‐ inflammatory activity by inhibiting the release of preformed andde novosynthesized mediators from human FcɛRI+cells.