Lamberts S W, Huizenga A T, de Lange P, de Jong F H, Koper J W
Department of Medicine, Erasmus University, Rotterdam, The Netherlands.
Steroids. 1996 Apr;61(4):157-60. doi: 10.1016/0039-128x(96)00005-0.
Recent studies demonstrate that primary (hereditary) abnormalities in the glucocorticoid receptor gene make 6.6% of the normal population relatively "hypersensitive" to glucocorticoids, while 2.3% are relatively "resistant." These abnormalities might explain why some individuals develop severe adverse effects during low dose glucocorticoid therapy, while others do not develop side effects even during long-term therapy with a much higher dose. Awareness of this heterogeneity in glucocorticoid sensitivity in the normal population might eventually allow the prediction of a "safe" dose of glucocorticoid in individual patients. "Resistance" to the beneficial clinical effects of glucocorticoid therapy in part of the patients with severe rheumatoid arthritis and asthma is probably rarely related to generalized primary (hereditary) glucocorticoid resistance. In the majority of patients this "resistance" seems to be acquired and localized to the sites of inflammation, where it reflects high local cytokine production, which interferes with glucocorticoid action. Recognition of localized, acquired glucocorticoid resistance is of great importance indicating as alternative drug therapy with other immune-modulating drugs like cyclosporin and methotrexate. Chronic high dose glucocorticoid treatment in such patients is ineffective in alleviating symptomatology, while generalized side effects occur, reflecting the patient's normal systemic sensitivity to these drugs.
近期研究表明，糖皮质激素受体基因的原发性（遗传性）异常使6.6%的正常人群对糖皮质激素相对“敏感”，而2.3%相对“抵抗”。这些异常可能解释了为什么一些个体在低剂量糖皮质激素治疗期间会出现严重不良反应，而另一些个体即使在高得多的剂量长期治疗期间也不会出现副作用。认识到正常人群中糖皮质激素敏感性的这种异质性最终可能有助于预测个体患者的糖皮质激素“安全”剂量。部分重症类风湿关节炎和哮喘患者对糖皮质激素治疗的有益临床效果“抵抗”，可能很少与全身性原发性（遗传性）糖皮质激素抵抗有关。在大多数患者中，这种“抵抗”似乎是后天获得的，且局限于炎症部位，这反映了局部细胞因子产生过多，从而干扰了糖皮质激素的作用。认识到局部获得性糖皮质激素抵抗非常重要，这表明可选用环孢素和甲氨蝶呤等其他免疫调节药物进行替代药物治疗。在此类患者中，长期高剂量糖皮质激素治疗无法有效缓解症状，反而会出现全身性副作用，这反映了患者对这些药物的正常全身敏感性。
