Division of Pediatric Allergy and Immunology, National Jewish Health, Denver, CO 80206, USA.
J Allergy Clin Immunol. 2012 Mar;129(3):687-693.e1. doi: 10.1016/j.jaci.2011.12.001. Epub 2012 Jan 10.
Blood tests are needed to identify steroid-resistant (SR) asthmatic patients early so that they can be managed with alternative anti-inflammatory therapy.
We sought to assess the usefulness of peripheral blood to predict steroid response in asthmatic patients.
Nineteen asthmatic patients with FEV(1) of less than 80% of predicted value were classified as SR or steroid sensitive (SS) based on change in lung FEV(1) percentage after 7 days of oral prednisone. Blood was collected at baseline (visit 1) and 30 days after prednisone administration (visit 3). PBMCs were cultured for 4 hours with or without 10(-7) mol/L dexamethasone, and cellular response to dexamethasone was determined by using real-time PCR based on expression analysis of steroid-regulated genes. Suppression of PHA-induced T-cell proliferation by dexamethasone was assessed.
Prednisone significantly improved FEV(1) percentages in SS asthmatic patients (mean ± SE: 17.5% ± 2.4%) but not SR asthmatic patients (0.8% ± 2.0%, P < .001). Before prednisone treatment, mitogen-induced kinase phosphatase 1 (P = .01) and IL-8 mRNA (P < .05) levels were significantly higher in PBMCs from SR asthmatic patients. TNF-α (P < .05) and IL-8 fold suppression by dexamethasone (P < .05) were significantly reduced in PBMCs from SR asthmatic patients. The expression of glucocorticoid receptor (GCR) β, but not GCR-α, was significantly increased in PBMCs of SR asthmatic patients (P = .01). The dexamethasone inhibitory concentration of 50% for PBMC proliferation was significantly higher for SR asthmatic patients (P < .05). These markers no longer differed between groups in PBMCs 30 days after prednisone administration. The composite score of assays at baseline before prednisone was significantly different between SR and SS asthmatic patients (P < .001).
PBMCs from SR asthmatic patients have higher baseline mitogen-induced kinase phosphatase 1, IL-8, and GCR-β mRNA levels; have a lower GCR-α/GCR-β mRNA ratio; are less responsive to suppression of TNF-α and IL-8 by dexamethasone; and require more dexamethasone to suppress T-cell proliferation compared with SS asthmatic patients.
需要通过血液检测来早期识别出类固醇抵抗（SR）的哮喘患者，以便对其采用替代抗炎疗法进行治疗。
我们旨在评估外周血在预测哮喘患者的类固醇反应中的作用。
19 名 FEV1（用力呼气量）低于预计值 80%的哮喘患者，根据口服泼尼松 7 天后肺 FEV1%的变化，被分为 SR 或类固醇敏感（SS）。在基线（第 1 次就诊）和泼尼松治疗 30 天后（第 3 次就诊）采集血液。用或不用 10（-7）mol/L 地塞米松培养 PBMC（外周血单个核细胞）4 小时，并通过实时 PCR 基于类固醇调节基因的表达分析来确定地塞米松对细胞的反应。评估地塞米松对 PHA 诱导的 T 细胞增殖的抑制作用。
SS 哮喘患者的泼尼松治疗后 FEV1%显著改善（平均±SE：17.5%±2.4%），而 SR 哮喘患者无改善（0.8%±2.0%，P<.001）。在接受泼尼松治疗前，SR 哮喘患者的 PBMC 中促分裂原诱导的蛋白激酶磷酸酶 1（P=0.01）和白细胞介素 8（IL-8）mRNA（P<.05）水平显著更高。SR 哮喘患者的 PBMC 中 TNF-α（P<.05）和地塞米松的 IL-8 抑制倍数（P<.05）显著降低。SR 哮喘患者的 PBMC 中糖皮质激素受体（GCR）β的表达显著增加（P=0.01），但 GCR-α的表达没有显著变化。SR 哮喘患者的 PBMC 增殖的地塞米松 50%抑制浓度显著更高（P<.05）。泼尼松治疗 30 天后，这些标志物在 PBMC 中的组间差异不再显著。泼尼松治疗前的基线综合评分在 SR 和 SS 哮喘患者之间有显著差异（P<.001）。
SR 哮喘患者的 PBMC 中促分裂原诱导的蛋白激酶磷酸酶 1、IL-8 和 GCR-β mRNA 水平较高；GCR-α/GCR-β mRNA 比值较低；对地塞米松抑制 TNF-α 和 IL-8 的反应较低；与 SS 哮喘患者相比，需要更多的地塞米松来抑制 T 细胞增殖。
