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 ef fective in the treatment of patients with seasonal and perennial rhini tis and some allergic skin disorders. Histamine and other chemical med iators are synthesized and immunologically released by human periphera l blood basophils and tissue mast cells (Fc epsilon RI+ cells). Object ive To evaluate the effects of loratadine and its main metabolite, des ethoxylcarbonyl-loratadine (des-loratadine), on the immunological rele ase of preformed (histamine and tryptase) and de novo synthesized medi ators (leukotriene C-4:LTC4 and prostaglandin D-2:PGD(2)) from human F c epsilon RI+ cells. Methods Human Fc epsilon RI+ cells purified from peripheral blood and from skin (HSMC) and lung tissue (HLMC) were prei ncubated with loratadine and des-loratadine before immunological chall enge with Der p 1 antigen or anti-Fc epsilon RI. The release of prefor med mediators (histamine and tryptase) and de novo synthesized eicosan oids was evaluated in the supernatants of human Fc epsilon RI+ cells. Results Preincubation (15 min, 37 degrees C) of purified (36-74%) baso phils 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, LT C4, and PGD(2) release from purified HLMC (16-68%) activated by anti-F c epsilon RI. Loratadine (3x10(-6)-10(-4)M) and des-loratadine caused concentration-dependent inhibition (10-40%) of histamine, tryptase, LT C4, and PGD(2) release from purified HSMC (24-72%) immunologically cha llenged with anti-Fc epsilon RI. Conclusion These results indicate tha t 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.