title: Immunosuppressive effects of azelastine hydrochloride on contact hypersensitivity and T-cell proliferative response: a comparative study with FK-506.
abstract: Azelastine hydrochloride (AZE) is an anti-allergic drug that inhibits the release of various chemical mediators from mast cells. We compared the immunosuppressive effects of AZE and FK-506 in vivo and in vitro. Topical application of AZE strongly inhibited the efferent phase of contact hypersensitivity, as did application of FK-506. In in vitro experiments, we found that 1) the suppression by AZE on interleukin (IL)-2 production from splenic T cells was partial and considerably large amounts of IL-2 were still produced, even in the presence of 10(-5) M of AZE, which was in sharp contrast to the observed marked inhibition of [3H]-TdR incorporation; 2) AZE significantly inhibited the phorbol myristate acetate-induced IL-2 responsiveness; 3) AZE did not inhibit the IL-2 receptor alpha expression of activated T cells; and 4) the significant inhibitory action was still observed even when AZE was added at 48 h after the initiation of culture. In regard to FK-506, we found that 1) FK-506 completely blocked the production of IL-2; 2) exogeneous IL-2 consistently restored the FK-506-induced inhibition; 3) FK-506 affected the phorbol myristate acetate-induced IL-2 responsiveness very little, if any; and 4) the significant suppression was observed only when FK-506 was added within 24 h after the initiation of culture. Thus, AZE exerts its in vitro immunosuppressive activity preferentially by interfering with the IL-2 responsiveness, with partial inhibition of IL-2 production. Conversely, FK-506 acts as a strong inhibitor of IL-2 production without a prominent effect on IL-2 responsiveness. The immunosuppressive activity of AZE shown in vitro may also be operative in vivo and may be applicable for topical use.
authors.affiliation: Department of Dermatology, Yamanashi Medical University, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Furue
authors.forename: A
authors.initials: A
authors.lastname: Osada
authors.forename: C H
authors.initials: CH
authors.lastname: Chang
authors.forename: K
authors.initials: K
authors.lastname: Tamaki
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D003877:Dermatitis, Contact / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D010793:Phthalazines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D015375:Receptors, Interleukin-2 / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D013601:T-Lymphocytes / Q000737:chemistry / Q000378:metabolism / Q000473:pathology*; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014316:Tritium
chemical_list: D001993:Bronchodilator Agents; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D010793:Phthalazines; D015375:Receptors, Interleukin-2; D014316:Tritium; D004247:DNA; D013755:Tetradecanoylphorbol Acetate; D013936:Thymidine; D016559:Tacrolimus; C020976:azelastine