title: Inhibition of allergen-induced histamine release from human basophils by cyclosporine A and FK-506.
abstract: A number of structurally different allergens trigger the release of mediators from basophils by cross-linking of IgE receptors. In this study, we analyzed the effects of cyclosporine A (CSA) and FK-506 on allergen-induced histamine release in human blood basophils obtained from birch- or grass-pollen-allergic donors (n = 12). Preincubation of basophils with CSA (0.003-3 microg/ml) or FK-506 (0.003-3 microg/ml) led to inhibition of histamine release induced by purified recombinant tree pollen allergens (r Bet v 1, r Bet v 2) and timothy grass pollen allergens (r Ph1 p 1, r Ph1 p 2, r Ph1 p 5). The effects of CSA and FK-506 were dose dependent, with IC50 values ranging between 0.03 and 0.3 microg/ml for both CSA and FK-506. Cyclosporine H, an inactive CSA analog, did not show any effect on allergen-induced histamine secretion. IgE dependency of the reaction was demonstrated in passive transfer experiments using highly enriched human basophils (> 95% pure) and specific IgE from a patient allergic to Bet v 2. In summary, our data show that CSA and FK-506 inhibit recombinant-allergen-induced histamine release from peripheral blood basophils in allergic donors.
authors.affiliation: Department of Internal Medicine I, University of Vienna, Austria.
authors.forename: W R
authors.initials: WR
authors.lastname: Sperr
authors.forename: H
authors.initials: H
authors.lastname: Agis
authors.forename: H
authors.initials: H
authors.lastname: Semper
authors.forename: R
authors.initials: R
authors.lastname: Valenta
authors.forename: M
authors.initials: M
authors.lastname: Susani
authors.forename: M
authors.initials: M
authors.lastname: Sperr
authors.forename: M
authors.initials: M
authors.lastname: Willheim
authors.forename: O
authors.initials: O
authors.lastname: Scheiner
authors.forename: E
authors.initials: E
authors.lastname: Liehl
authors.forename: K
authors.initials: K
authors.lastname: Lechner
authors.forename: P
authors.initials: P
authors.lastname: Valent
mesh_terms: D000328:Adult; D000485:Allergens / Q000008:administration & dosage*; D001249:Asthma / Q000276:immunology; D001491:Basophils / Q000187:drug effects* / Q000276:immunology*; D003233:Conjunctivitis, Allergic / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007116:Immunization, Passive; D007073:Immunoglobulin E / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology*
chemical_list: D000485:Allergens; D007166:Immunosuppressive Agents; D007073:Immunoglobulin E; D016572:Cyclosporine; D016559:Tacrolimus