Lane S J, Lee T H
Dept of Allergy and Allied Respiratory Disorders, United Medical and Dental Schools, Guy's Hospital, London, UK.
Monaldi Arch Chest Dis. 1993 Dec;48(6):635-9.
Glucocorticosteroids (GCS) are the most effective treatment for bronchial asthma. Their mechanism of action, however, remains unknown, and a small proportion of asthmatic sufferers do not respond to their effects. GCS resistance in bronchial asthma may be secondary to altered bioavailability, a consistent polymorphism in the glucocorticoid receptor (GR), defective interaction with other transcription factors and/or deoxyribonucleic acid (DNA), or to a specific gene defect. Corticosteroid resistant bronchial asthma (CR asthma) cannot be explained on the basis of altered pharmacokinetics, or defective nuclear translocation or ligand binding of the GR, in CR subjects. Furthermore, peripheral blood monocytes (PBM) derived from asthmatic subjects generate a 3 Kd activity, which is proinflammatory in vitro for neutrophils and which is selectively inhibited by GCS in corticosteroid sensitive (CS) asthmatic subjects, with no inhibition seen in the CR group, suggesting a specific gene(s) defect.
糖皮质激素（GCS）是治疗支气管哮喘最有效的药物。然而，其作用机制尚不清楚，且一小部分哮喘患者对其治疗无反应。支气管哮喘中的GCS抵抗可能继发于生物利用度改变、糖皮质激素受体（GR）的一致多态性、与其他转录因子和/或脱氧核糖核酸（DNA）的相互作用缺陷，或特定基因缺陷。在CR受试者中，皮质类固醇抵抗性支气管哮喘（CR哮喘）无法用改变的药代动力学、GR的核转位缺陷或配体结合缺陷来解释。此外，哮喘患者外周血单核细胞（PBM）产生一种3 Kd活性，该活性在体外对中性粒细胞具有促炎作用，并且在皮质类固醇敏感（CS）哮喘患者中被GCS选择性抑制，而在CR组中未见抑制，提示存在特定基因缺陷。
