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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Selective resistance to different glucocorticoids in severe autoimmune disorders.
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Selective resistance to different glucocorticoids in severe autoimmune disorders.

机译：在严重的自身免疫性疾病中对不同糖皮质激素的选择性耐药。

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摘要

Resistance to glucocorticoids often occurs in patients with severe inflammatory disorders. Occasionally, this resistance could be overcome by switching to a different glucocorticoid, but the mechanisms of this selectivity are not clear. We studied this condition in three patients with severe inflammatory disorders, who responded satisfactorily to betamethasone, but could not be switched to equipotent doses of methylprednisolone or prednisone. While betamethasone displayed similar activity on lymphocyte proliferation in cells obtained from the three patients and controls, higher concentrations of methylprednisolone were needed to inhibit proliferation in patients' cells. In a competition study, the concentration of methylprednisolone that inhibited 50% of specific [(3)H]dexamethasone binding was increased in patients' lymphocytes. Higher Rhodamine-123 efflux was demonstrated in CD4 T cells from two patients, suggesting that an increased activity of membrane transporters could be responsible for the selective response to different glucocorticoids, even if P-glycoprotein and MRP1 expression was not increased.
机译：患有严重炎性疾病的患者经常发生对糖皮质激素的耐药性。有时，可以通过改用其他糖皮质激素来克服这种耐药性，但这种选择性的机制尚不清楚。我们在三例严重的炎症性疾病患者中研究了这种情况，这些患者对倍他米松的治疗满意，但无法转换为等剂量的甲基强的松龙或泼尼松。虽然倍他米松对从这三名患者和对照组获得的细胞的淋巴细胞增殖表现出相似的活性，但需要更高浓度的甲基泼尼松龙来抑制患者细胞的增殖。在一项竞争研究中，抑制患者淋巴细胞中50％的特定[（3）H]地塞米松特异性结合的甲基强的松龙的浓度增加了。在两名患者的CD4 T细胞中证实了更高的若丹明123外流，这表明膜转运蛋白的活性增加可能是对不同糖皮质激素的选择性反应的原因，即使P-糖蛋白和MRP1表达没有增加。

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