Hagan J B, Kita H, Gleich G J
Department of Immunology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Clin Exp Allergy. 1998 Aug;28(8):999-1006. doi: 10.1046/j.1365-2222.1998.00363.x.
Inhaled glucocorticoids are commonly employed to treat patients with asthma. Eosinophils are important effector cells in the pathogenesis of asthma, and, in vitro, glucocorticoids modulate eosinophil viability.
Using this glucocorticoid inhibition of eosinophil viability, we compared the in vitro potencies of several inhaled glucocorticoids with particular attention to fluticasone 17-propionate.
Eosinophils from normal or mildly atopic donors were purified, cultured with cytokines and glucocorticoids, and on day 4, after staining with propidium iodide, analysed by flow cytometry.
Eosinophil viability was prolonged by interleukin (IL)-5 in a concentration-dependent manner; in contrast, dexamethasone inhibited the IL-5 effect. Fluticasone 17-propionate, 1.0-1000 nM, also inhibited the IL-5 effect in a concentration-dependent manner; interestingly, at 0.1 nM fluticasone 17-propionate modestly, but significantly, enhanced eosinophil survival. High concentrations of IL-5 and granulocyte-macrophage colony-stimulating factor essentially completely overcame the inhibitory effect of 1000 nM fluticasone 17-propionate on eosinophil survival. In contrast, although interferon-gamma-mediated eosinophil viability was inhibited by 1.0-1000 nM fluticasone 17-propionate, this inhibition was not overcome by increased concentrations of interferon-gamma. Comparison of the glucocorticoid inhibition of eosinophil viability in the presence of 10 pg/mL IL-5 resulted in these drug IC50 values (in nM): fluticasone 17-propionate, 1.3; budesonide, 8.5; triamcinolone acetonide, 25; flunisolide, 32; dexamethasone, 94; beclomethasone 17-monopropionate, 210; beclomethasone 17,21-dipropionate, 290; and hydrocortisone, >1000.
Fluticasone 17-propionate's effect on cytokine-mediated eosinophil viability is similar qualitatively to other glucocorticoid preparations. However, quantitatively, fluticasone 17-propionate has the most potent suppressive effects on IL-5 mediated eosinophil viability among the currently available inhaled glucocorticoids in the United States.
吸入性糖皮质激素常用于治疗哮喘患者。嗜酸性粒细胞是哮喘发病机制中的重要效应细胞，在体外，糖皮质激素可调节嗜酸性粒细胞的活力。
利用糖皮质激素对嗜酸性粒细胞活力的抑制作用，比较几种吸入性糖皮质激素的体外效力，特别关注丙酸氟替卡松。
从正常或轻度特应性供体中纯化嗜酸性粒细胞，与细胞因子和糖皮质激素一起培养，在第4天，用碘化丙啶染色后，通过流式细胞术进行分析。
白细胞介素（IL）-5以浓度依赖的方式延长嗜酸性粒细胞的存活时间；相反，地塞米松抑制IL-5的作用。1.0 - 1000 nM的丙酸氟替卡松也以浓度依赖的方式抑制IL-5的作用；有趣的是，在0.1 nM时，丙酸氟替卡松适度但显著地提高了嗜酸性粒细胞的存活率。高浓度的IL-5和粒细胞-巨噬细胞集落刺激因子基本上完全克服了1000 nM丙酸氟替卡松对嗜酸性粒细胞存活的抑制作用。相比之下，虽然1.0 - 1000 nM的丙酸氟替卡松抑制了干扰素-γ介导的嗜酸性粒细胞活力，但这种抑制作用不会因干扰素-γ浓度的增加而被克服。在存在10 pg/mL IL-5的情况下比较糖皮质激素对嗜酸性粒细胞活力的抑制作用，得出这些药物的半数抑制浓度（IC50）值（以nM为单位）：丙酸氟替卡松，1.3；布地奈德，8.5；曲安奈德，25；氟尼缩松，32；地塞米松，94；倍氯米松17-单丙酸酯，210；倍氯米松17,21-二丙酸酯，290；以及氢化可的松，>1000。
丙酸氟替卡松对细胞因子介导的嗜酸性粒细胞活力的影响在质量上与其他糖皮质激素制剂相似。然而，在数量上，在美国目前可用的吸入性糖皮质激素中，丙酸氟替卡松对IL-5介导的嗜酸性粒细胞活力具有最强的抑制作用。
