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    • 1. 发明授权
    • Methods and compositions for modulating responsiveness to corticosteroids
    • 调节对皮质类固醇反应的方法和组合物
    • US6054487A
    • 2000-04-25
    • US820692
    • 1997-03-18
    • Les SekutAdam CarterTariq GhayurSubhashis BanerjeeDaniel E. Tracey
    • Les SekutAdam CarterTariq GhayurSubhashis BanerjeeDaniel E. Tracey
    • A61K31/18
    • A61K31/18
    • Method for modulating responsiveness to corticosteroids in a subject are provided. In the method of the invention, an agent which antagonizes a factor that regulates production of IFN-.gamma. in the subject is administered to the subject in combination with a corticosteroid such that responsiveness of the subject to the corticosteroid is modulated as compared to when a corticosteroid alone is administered to the subject. In one embodiment, the agent is an interferon-.gamma. inducing factor (IGIF) antagonist. In another embodiment, the agent is an interleukin-12 (IL-12) antagonist. In a preferred embodiment, the agent is an inhibitor of a caspase family protease, preferably an ICE inhibitor. In another preferred embodiment, the agent is an anti-IL-12 monoclonal antibody. Other preferred agents include phosphodiesterase IV inhibitors and beta-2 agonists. The methods of the invention can be used in the treatment of a variety of inflammatory and immunological diseases and disorders. Pharmaceutical compositions comprising an agent which antagonizes a factor that regulates production of IFN-.gamma. in a subject, a corticosteroid and a pharmaceutically acceptable carrier are also provided. A preferred composition comprises an ICE inhibitor, a corticosteroid and a pharmaceutically acceptable carrier.
    • 提供了调节受试者对皮质类固醇的反应性的方法。 在本发明的方法中,将拮抗受试者中IFN-γ产生的因子拮抗的药物与皮质类固醇组合给予受试者,使得受试者对皮质类固醇的反应性与皮质类固醇相比被调节 单独对受试者施用。 在一个实施方案中,所述试剂是干扰素-γ诱导因子(IGIF)拮抗剂。 在另一个实施方案中,该药剂是白细胞介素-12(IL-12)拮抗剂。 在优选的实施方案中,所述试剂是半胱天冬酶家族蛋白酶,优选ICE抑制剂的抑制剂。 在另一个优选的实施方案中,所述试剂是抗IL-12单克隆抗体。 其它优选的试剂包括磷酸二酯酶IV抑制剂和β-2激动剂。 本发明的方法可用于治疗各种炎症和免疫疾病和病症。 还提供了包含拮抗受试者中的IFN-γ生成因子,皮质类固醇和药学上可接受的载体的药剂的药物组合物。 优选的组合物包含ICE抑制剂,皮质类固醇和药学上可接受的载体。