Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.
Clin Exp Rheumatol. 2009 Jul-Aug;27(4 Suppl 55):S152-8.
Glucocorticoids (GCs) have powerful and potent anti-inflammatory and immunomodulatory effects and are widely established in regard to the treatment of rheumatism and other diseases. In rheumatoid arthritis (RA), GCs are used systemically at several different dosages and/or local (intraarticular) therapy. They have been shown to exert strong short-term anti-inflammatory effects but also long-term positive effects on radiographic progression of the disease. In comparison, patients with ankylosing spondylitis (AS) are considered to be less responsive to GC therapy than patients with RA, although controlled studies on the effects of low-dose GCs in AS are lacking. In AS, GCs are mainly used for local therapy and occasionally for systemic pulse therapy only. The underlying mechanisms for these differences are unclear. GCs act on primary and secondary immune cells via different mechanisms of action: cytosolic GC receptor (cGCR)-mediated genomic and non-genomic effects, membrane-bound GC receptor (mGCR)-mediated non-genomic effects and - as achieved at very high concentrations - non-specific non-genomic effects. The phenomenon of GC resistance is also known in RA. Several different mechanisms may mediate this phenomenon; among them are alterations in number, binding affinity or phosphorylation status of the GCR, polymorphic changes and/or over-expression of chaperones/ co-chaperones, increased expression of inflammatory transcription factors, the multidrug resistance pump, over-expression of the GCR beta isoform, alteration in the expression of mGCR and imbalance of 11beta-hydroxysteroid dehydrogenase type 1 & 2 activity. Translation of insights on GC action and resistance obtained in RA to AS may contribute to a better understanding of the pathophysiology of both diseases.
糖皮质激素（GCs）具有强大而有效的抗炎和免疫调节作用，在治疗风湿病和其他疾病方面得到了广泛的应用。在类风湿关节炎（RA）中，GC 以几种不同的剂量全身使用和/或局部（关节内）治疗。它们已被证明具有强烈的短期抗炎作用，但也对疾病的放射学进展有长期的积极影响。相比之下，强直性脊柱炎（AS）患者被认为对 GC 治疗的反应不如 RA 患者，尽管缺乏关于 AS 中低剂量 GCs 作用的对照研究。在 AS 中，GC 主要用于局部治疗，偶尔也用于全身脉冲治疗。这些差异的潜在机制尚不清楚。GC 通过不同的作用机制作用于初级和次级免疫细胞：细胞溶质 GC 受体（cGCR）介导的基因组和非基因组效应、膜结合 GC 受体（mGCR）介导的非基因组效应以及 - 在非常高的浓度下 - 非特异性非基因组效应。GC 抵抗现象在 RA 中也存在。几种不同的机制可能介导这种现象；其中包括 GCR 数量、结合亲和力或磷酸化状态的改变、多态性变化和/或伴侣/共伴侣的过度表达、炎症转录因子表达增加、多药耐药泵、GCR β 同工型过度表达、mGCR 表达改变以及 11β-羟甾醇脱氢酶 1 和 2 活性的失衡。将在 RA 中获得的关于 GC 作用和抵抗的见解转化为 AS，可能有助于更好地理解这两种疾病的病理生理学。
