Lane S J, Lee T H
Department of Allergy and Respiratory Medicine, Guy's Hospital, London, UK.
Int Arch Allergy Immunol. 1997 May-Jul;113(1-3):193-5. doi: 10.1159/000237544.
Corticosteroid-resistant (CR) asthma is associated with disease chronicity, a more frequent family history of asthma and impaired in vitro and in vivo responsiveness of peripheral blood mononuclear cells to the suppressive effects of glucocorticoids. CR asthma is associated with normal suppression of the hypothalamic-pituitary-adrenal axis and of biochemical indices of bone turnover by dexamethasone, indicating that the phenomenon of glucocorticoid resistance is specific to inflammatory leukocytes and that these patients are equally at risk of developing 'cushingoid' side effects. We have been unable to detect altered bioavailability of administered glucocorticoid, impaired ligand binding or nuclear translocation of the activated glucocorticoid receptor (GR) complex or structural abnormalities of the GR cDNA in our population of CR asthmatics. We have recently demonstrated that CR asthma is associated with decreased GR and increased AP-1 (Fos; Jun) DNA binding in peripheral blood mononuclear cells as compared to corticosteroid-sensitive asthma. These results highlight the central role of the AP-1/GR interactions in glucocorticoid action in CR asthma.
糖皮质激素抵抗（CR）性哮喘与疾病的慢性病程、更常见的哮喘家族史以及外周血单核细胞在体外和体内对糖皮质激素抑制作用的反应性受损有关。CR哮喘与下丘脑-垂体-肾上腺轴的正常抑制以及地塞米松对骨转换生化指标的正常抑制有关，这表明糖皮质激素抵抗现象是炎症白细胞特有的，并且这些患者发生“库欣样”副作用的风险相同。在我们的CR哮喘患者群体中，我们未能检测到所给予糖皮质激素的生物利用度改变、配体结合受损或活化的糖皮质激素受体（GR）复合物的核转位，也未检测到GR cDNA的结构异常。我们最近证明，与糖皮质激素敏感哮喘相比，CR哮喘与外周血单核细胞中GR减少和AP-1（Fos；Jun）DNA结合增加有关。这些结果突出了AP-1/GR相互作用在CR哮喘糖皮质激素作用中的核心作用。
