Department of Rheumatology and Clinical Immunology, Charité - Universitätsmedizin Berlin, Campus Mitte, Berlin, Germany.
Clin Exp Rheumatol. 2011 Sep-Oct;29(5 Suppl 68):S13-8. Epub 2011 Oct 21.
Exogenous glucocorticoids (GCs) are used as anti-inflammatory and immunosuppressive drugs in the treatment of a wide range of rheumatic and other inflammatory diseases. GCs exert their immunosuppressive, anti-inflammatory and anti-allergic effects on primary and secondary immune cells, tissues and organs via different mechanisms of action in a dose-dependent manner. However, their pleiotropic effects also lead to numerous adverse effects such as unwanted metabolic effects and osteoporosis. The mechanisms of action include the classical genomic mechanism resulting from activation of the cytosolic glucocorticoid receptor (cGCR), non-specific, non-genomic effects caused by interactions with cellular membranes, secondary non-genomic effects initiated by the cGCR and specific interactions with a membrane-bound glucocorticoid receptor (mGCR). Optimised glucocorticoids, such as selective glucocorticoid receptor agonists, are being developed to minimise the adverse effects many patients experience, especially if GCs are given at higher dosages over longer periods of time. Immunostimulatory effects of low concentrations of endogenous glucocorticoids and the influence of pre-receptor metabolism appear of interest for further investigation. The most important approach to optimise the risk-benefit ratio of GCs is to understand in more detail how the molecular mechanisms of genomic and non-genomic GC actions - and their dose-dependency - mediate the clinically wanted benefits but also the known adverse effects.
外源性糖皮质激素（GCs）被用作治疗广泛的风湿性和其他炎症性疾病的抗炎和免疫抑制剂。GCs 通过不同的作用机制，以剂量依赖的方式对初级和次级免疫细胞、组织和器官发挥其免疫抑制、抗炎和抗过敏作用。然而，它们的多效性作用也导致了许多不良反应，如代谢异常和骨质疏松症。作用机制包括激活胞质糖皮质激素受体（cGCR）导致的经典基因组机制、与细胞膜相互作用引起的非特异性、非基因组效应、由 cGCR 引发的二次非基因组效应以及与膜结合糖皮质激素受体（mGCR）的特异性相互作用。正在开发优化的糖皮质激素，如选择性糖皮质激素受体激动剂，以最小化许多患者经历的不良反应，特别是如果在较长时间内以较高剂量给予 GCs。内源性糖皮质激素的低浓度的免疫刺激作用和受体前代谢的影响似乎值得进一步研究。优化 GCs 的风险效益比的最重要方法是更详细地了解基因组和非基因组 GC 作用的分子机制及其剂量依赖性如何介导临床上所需的益处，以及已知的不良反应。
