Department of Pathology and Laboratory Medicine, Western University, 1151 Richmond Street, Dental Science Building Rm. 4037, London, Ontario, N6A 5C1, Canada.
Department of Emergency Medicine and School of Public Health, University of Alberta, Edmonton, Alberta, Canada.
BMC Immunol. 2020 Oct 19;21(1):54. doi: 10.1186/s12865-020-00383-8.
Corticosteroids (CS)s suppress cytokine production and induce apoptosis of inflammatory cells. Prednisone and dexamethasone are oral CSs prescribed for treating asthma exacerbations. While prednisone is more commonly prescribed, dexamethasone is long acting and a more potent glucocorticoid receptor (GR) agonist. It can be administered as a one or two dose regime, unlike the five to seven days required for prednisone, a feature that increases compliance. We compared the relative ability of these two oral CSs to suppress type 2 inflammation. Since progesterone has affinity for the GR and women are more likely to relapse following an asthma exacerbation, we assessed its influence on CS action.
Dexamethasone suppressed the level of IL-5 and IL-13 mRNA within Th2 cells with ~ 10-fold higher potency than prednisolone (the active form of prednisone). Dexamethasone induced a higher proportion of apoptotic and dying cells than prednisolone, at all concentrations examined. Addition of progesterone reduced the capacity of both CS to drive cell death, though dexamethasone maintained significantly more killing activity. Progesterone blunted dexamethasone-induction of FKBP5 mRNA, indicating that the mechanism of action was by interference of the CS:GR complex.
Dexamethasone is both more potent and effective than prednisolone in suppressing type 2 cytokine levels and mediating apoptosis. Progesterone attenuated these anti-inflammatory effects, indicating its potential influence on CS responses in vivo. Collectively, our data suggest that when oral CS is required, dexamethasone may be better able to control type 2 inflammation, eliminate Th2 cells and ultimately lead to improved long-term outcomes. Further research in asthmatics is needed.
皮质类固醇（CS）抑制细胞因子的产生并诱导炎症细胞凋亡。泼尼松和地塞米松是用于治疗哮喘发作的口服 CS。虽然泼尼松更常被开处方，但地塞米松作用时间更长，是一种更有效的糖皮质激素受体（GR）激动剂。它可以作为单次或两次剂量方案给药，与泼尼松需要五到七天的时间不同，这一特点提高了顺应性。我们比较了这两种口服 CS 抑制 2 型炎症的相对能力。由于孕激素对 GR 有亲和力，并且女性在哮喘发作后更有可能复发，因此我们评估了它对 CS 作用的影响。
地塞米松抑制 Th2 细胞中 IL-5 和 IL-13 mRNA 的水平，其效力比泼尼松龙（泼尼松的活性形式）高约 10 倍。地塞米松诱导比泼尼松龙更高比例的凋亡和死亡细胞，在所有检查的浓度下都是如此。添加孕激素降低了两种 CS 驱动细胞死亡的能力，尽管地塞米松仍然保持着显著更高的杀伤活性。孕激素削弱了地塞米松诱导的 FKBP5 mRNA，表明作用机制是通过干扰 CS:GR 复合物。
地塞米松在抑制 2 型细胞因子水平和介导细胞凋亡方面比泼尼松龙更有效和更有效。孕激素减弱了这些抗炎作用，表明其对 CS 在体内反应的潜在影响。总之，我们的数据表明，当需要口服 CS 时，地塞米松可能更能控制 2 型炎症，消除 Th2 细胞，并最终导致改善的长期结果。需要在哮喘患者中进行进一步的研究。
