吸入布地奈德福莫特罗对于哮喘患者循环系统淋巴细胞的快速全身抗炎作用
2013/12/16
背景和目的：吸入性糖皮质激素和长效β2受体激动剂减少气道炎症。是否这个影响是以药物的局部作用为基础或者是由于在循环外周血淋巴细胞的全身作用还不是很清楚。我们估计是否是吸入性布地奈德和或福莫特罗减轻了循环外周血淋巴细胞的活动。
方法：安慰剂对照的交叉设计，包括健康的（n=10）或轻度哮喘男性（n=8）。在早晨08:00吸入药物之前采集血液，在08:30单独或者吸入合剂药物（安慰剂，布地奈德400μg，福莫特罗12μg）。在09:00，09:30，12:30和第二天的上午09:30采集4个时段的血样本。糖皮质激素受体 NFκB和IκB的活性由分离的淋巴细胞决定。脂多糖（LPS 10 μg/mL）在24小时里刺激淋巴细胞，测定白介素（IL）-1，IL-6，IL-8，肿瘤坏死因子 (TNF)-α，趋化因子的水平。超过24小时植物血细胞凝集素(PHA 10 μg/mL)增加了淋巴细胞的增值。
结果：药物联合起来，在30分钟内协同的活化糖皮质激素受体但是不能减轻NFκB和IκB的活性。吸入性布地奈德显著的减少脂多糖诱导的IL-1β, IL-6, IL-8和TNF-α等分泌物，而吸入性福莫特罗没有这样的效果，然而当联合起来，布地奈德的抑制作用显著地被福莫特罗增加。PHA诱发的增值可被药物单独和合剂二者减少。
结论：布地奈德和福莫特罗合剂可能通过对局部和全身的效果减少气道炎症以及外周淋巴细胞的免疫反应。
（苏新明 中国医科大学附属一院呼吸科 110001 摘译）
（Rüdiger JJ, Gencay M, Yang JQ, et al. Respirology. 2013 Jul;18(5):840-7）
Fast beneficial systemic anti-inflammatory effects of inhaled budesonide and formoterol on circulating lymphocytes in asthma
Abstract
Background and Objective: Inhaled glucocorticoids and long acting β2 -agonists reduce airway inflammation. It is unclear if this effect is based on the local action of the drugs or is due to a systemic effect on circulating peripheral blood lymphocytes. We assessed whether inhaled budesonide and/or formoterol modify the activity of circulating peripheral blood lymphocytes.
Methods: Placebo controlled crossover design, including healthy (n = 10) or mild asthmatic males (n = 8). Blood was collected in the morning at 08:00 before drug inhalation, and drugs (placebo, budesonide 400 μg, formoterol 12 μg) were inhaled alone or in combination at 08:30. Four more blood samples were collected after inhalation at 09:00, 09:30, 12:30 and at 09:30 am on the following day. The activity of the glucocorticoid receptor, NFκB and IκB was determined in isolated lymphocytes. Lymphocytes were stimulated with lipopolysaccharide (LPS 10 μg/mL) for 24 h and interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, eotaxin level were determined. Lymphocyte proliferation was induced by phytohaemagglutinin (PHA 10 μg/mL) over 24 h.
Results: When combined, the drugs synergistically activated the glucocorticoid receptor within 30 min but did not modify NFκB or IκB activity. Inhaled budesonide significantly reduced LPS-induced IL-1β, IL-6, IL-8 and TNF-α secretion, while inhaled formoterol had no such effect; however when combined, the inhibitory effect of budesonide was significantly increased by formoterol. PHA-induced proliferation was reduced by both drugs alone and in combination.
Conclusions: Combined budesonide and formoterol may reduce airway inflammation and immune reactivity of circulating lymphocytes through its local and systemic effects.
Rüdiger JJ, Gencay M, Yang JQ, et al. Respirology. 2013 Jul;18(5):840-7
上一篇：
压力定量吸入器吸入丙酸氟替卡松和富马酸福莫特罗固定剂量复方制剂(FP/FORM) 治疗哮喘的预算影响分析
下一篇：
接受吸入性糖皮质激素治疗的患者升高的骨膜蛋白水平与更严重的气流受限相关
