Loratadine and desethoxylcarbonyl-loratadine inhibit the immunological release of mediators from human Fc epsilon RI+ cells

Background Loratadine, a novel histamine Hi-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 (Fc epsilon RI+ 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:LTC4 and prostaglandin D-2:PGD(2)) from human Fc epsilon RI+ cells. Methods Human Fc epsilon RI+ 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-Fc epsilon RI. The release of preformed mediators (histamine and tryptase) and de novo synthesized eicosanoids was evaluated in the supernatants of human Fc epsilon RI+ cells. Results Preincubation (15 min, 37 degrees C) of purified (36-74%) basophils with loratadine (3x10(-6)-10(-4)M) and des-loratadine before Der p 1 antigen or anti-Fc epsilon RI challenge concentration-dependently (5-40%) inhibited the release of histamine and LTC4. Loratadine (3x10(-6)-10(-4)M) and des-loratadine also inhibited (10-40%) histamine, LTC4, and PGD(2) release from purified HLMC (16-68%) activated by anti-Fc epsilon RI. Loratadine (3x10(-6)-10(-4)M) and des-loratadine caused concentration-dependent inhibition (10-40%) of histamine, tryptase, LTC4, and PGD(2) release from purified HSMC (24-72%) immunologically challenged with anti-Fc epsilon RI. Conclusion These results indicate that loratadine and its main metabolite have antiinflammatory activity by inhibiting the release of preformed and de novo synthesized mediators from human Fc epsilon RI+ cells.