Soma Tomoyuki, Takaku Yotaro, Kobayashi Takehito, Hagiwara Koichi, Kanazawa Minoru, Uematsu Kazutsugu, Nagata Makoto
Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan.
Int Arch Allergy Immunol. 2008;146 Suppl 1:22-7. doi: 10.1159/000126056. Epub 2008 May 27.
The use of a budesonide (BUD)/formoterol (FOR) combination (Symbicort) for both maintenance and reliever therapy reduces the exacerbation of asthma better than the traditional fixed-dose regimens. In the early stage of exacerbation, the combination therapy could intervene with the development of subsequent airway inflammation. The objective of the study was to evaluate whether in the early stage of cell activation the use of BUD/FOR combination would modify the adhesion of eosinophils or production of cytokines from mononuclear cells.
Human peripheral blood eosinophils, pretreated with BUD (0.1 microM), FOR (0.1 microM) or BUD/FOR combination for 30 min at 37 degrees C, were stimulated with IL-5, leukotriene D4 or phorbol myristate acetate, and eosinophil adhesion was evaluated using an eosinophil peroxidase assay. BUD (0.1 microM), FOR (0.1 microM) or BUD/FOR combination was added to the peripheral blood mononuclear cells stimulated with ionomycin plus phorbol myristate acetate. Concentrations of IL-5 and RANTES in the cell supernatant were measured using ELISA.
BUD, FOR or BUD/FOR combination did not modify the eosinophil adhesion induced by any stimulators. In contrast, BUD or BUD/FOR combination significantly reduced the productions of IL-5 and RANTES in peripheral blood mononuclear cells (BUD: p < 0.0001, p = 0.027 vs. control; BUD/FOR: p < 0.0001, p = 0.031 vs. control) when the drugs were added 15 min, but not 4 h, following cell stimulation.
In the early stage of exacerbation of asthma, inhaled BUD may suppress the progression of the allergic inflammatory cascade by inhibiting the mononuclear cells. These results also underline the importance of using BUD in rescue inhaler.
布地奈德（BUD）/福莫特罗（FOR）联合制剂（信必可都保）用于维持治疗和缓解治疗，在减轻哮喘恶化方面比传统固定剂量方案效果更佳。在恶化的早期阶段，联合治疗可干预随后气道炎症的发展。本研究的目的是评估在细胞激活的早期阶段，使用BUD/FOR联合制剂是否会改变嗜酸性粒细胞的黏附或单核细胞细胞因子的产生。
将人外周血嗜酸性粒细胞在37℃下用BUD（0.1微摩尔）、FOR（0.1微摩尔）或BUD/FOR联合制剂预处理30分钟，然后用白细胞介素-5、白三烯D4或佛波醇肉豆蔻酸酯乙酸盐刺激，使用嗜酸性粒细胞过氧化物酶测定法评估嗜酸性粒细胞黏附。将BUD（0.1微摩尔）、FOR（0.1微摩尔）或BUD/FOR联合制剂添加到用离子霉素加佛波醇肉豆蔻酸酯乙酸盐刺激的外周血单核细胞中。使用酶联免疫吸附测定法测量细胞上清液中白细胞介素-5和RANTES的浓度。
BUD、FOR或BUD/FOR联合制剂均未改变任何刺激物诱导的嗜酸性粒细胞黏附。相比之下，当在细胞刺激后15分钟而非4小时添加药物时，BUD或BUD/FOR联合制剂显著降低了外周血单核细胞中白细胞介素-5和RANTES的产生（BUD：与对照组相比，p < 0.0001，p = 0.027；BUD/FOR：与对照组相比，p < 0.0001，p = 0.031）。
在哮喘恶化的早期阶段，吸入BUD可能通过抑制单核细胞来抑制过敏性炎症级联反应的进展。这些结果也强调了在急救吸入器中使用BUD的重要性。
