Department of Pharmacology, University of Melbourne, Parkville, Victoria 3010, Australia.
Drug Discov Today. 2012 Sep;17(17-18):1031-8. doi: 10.1016/j.drudis.2012.05.011. Epub 2012 May 31.
Synthetic glucocorticoids are among the most commonly used prescription medicines. Nevertheless, their clinical efficacy is accompanied by dose- and indication-limiting acute and chronic adverse effects. Intrinsic or acquired resistance to glucocorticoid actions may also limit clinical efficacy. In chronic inflammatory conditions there has been a considerable focus on understanding mechanism(s) of resistance in cells with a primary immune and/or inflammatory function. However, it has become increasingly accepted that a substantial part of the efficacy of glucocorticoid treatments derives from actions on 'structural' cell types (smooth muscle, fibroblasts, epithelia). In this article we review the mechanism of action of glucocorticoids on structural cells and contrast knowledge of resistance mechanisms between structural and inflammatory cell types, using asthma as an exemplar chronic inflammatory condition associated with glucocorticoid resistance.
合成糖皮质激素是最常用的处方药之一。然而，它们的临床疗效伴随着剂量和适应证限制的急性和慢性不良反应。糖皮质激素作用的内在或获得性抵抗也可能限制临床疗效。在慢性炎症性疾病中，人们已经相当关注原发性免疫和/或炎症功能细胞中抵抗机制的理解。然而，人们越来越接受这样一种观点，即糖皮质激素治疗的大部分疗效来自于对“结构性”细胞类型（平滑肌、成纤维细胞、上皮细胞）的作用。在本文中，我们综述了糖皮质激素对结构性细胞的作用机制，并对比了结构性和炎症性细胞类型之间抵抗机制的知识，以哮喘为例，哮喘是一种与糖皮质激素抵抗相关的慢性炎症性疾病。
