Linden M, Svensson C, Andersson E, Andersson M, Greiff L, Persson C G
Experimental Medicine, AstraZeneca R&D, Lund, Sweden.
Am J Respir Crit Care Med. 2000 Nov;162(5):1705-8. doi: 10.1164/ajrccm.162.5.9910094.
The nasal antiinflammatory effects produced by maintenance treatment with topical steroids include reduced production of cytokines. The present study explored nasal mucosal effects induced during the first 9 h after a single dose of topical budesonide. Nine subjects with allergic rhinitis due to birch or timothy pollen were given budesonide (256 microg; Rhinocort Aqua) or placebo in a double-blind, randomized, crossover (4 wk washout) manner. Nasal allergen challenges were performed 30 min after the steroid/placebo pretreatment. Before and 30 min, 1, 3, 5, 7, and 9 h after challenge, filter paper strips were placed on the nasal septum and inferior turbinates for 10 min to sample undiluted mucosal fluids. Strips were then extracted in 1 ml buffer for cytokine analysis (ELISA). Allergen challenge produced acute nasal symptoms that peaked at 30 min and then tapered off. Conversely, both GM-CSF and IL-5 were increased only at 3, 5, 7 and 9 h (p < 0.05 compared with baseline). Budesonide did not affect the nasal symptoms but inhibited (p < 0. 05; compared with placebo treatment) the allergen challenge-induced mucosal output of GM-CSF and IL-5. These data demonstrate that GM-CSF and IL-5 are induced in a nonsymptomatic, late phase response to nasal allergen challenge, and that this cytokine response is prevented by single dose budesonide pretreatment.
局部用类固醇维持治疗产生的鼻抗炎作用包括细胞因子产生减少。本研究探讨了单次给予局部用布地奈德后最初9小时内诱导的鼻黏膜效应。9名因桦树或梯牧草花粉引起变应性鼻炎的受试者,以双盲、随机、交叉(4周洗脱期)方式给予布地奈德(256微克;雷诺考特)或安慰剂。在类固醇/安慰剂预处理后30分钟进行鼻过敏原激发试验。在激发试验前以及激发试验后30分钟、1、3、5、7和9小时,将滤纸置于鼻中隔和下鼻甲上10分钟,以采集未稀释的黏膜液样本。然后将滤纸条在1毫升缓冲液中提取用于细胞因子分析(酶联免疫吸附测定)。过敏原激发试验产生急性鼻症状,在30分钟时达到峰值,然后逐渐减轻。相反,粒细胞-巨噬细胞集落刺激因子(GM-CSF)和白细胞介素-5(IL-5)仅在3、5、7和9小时增加(与基线相比,p<0.05)。布地奈德不影响鼻症状,但抑制(与安慰剂治疗相比,p<0.05)过敏原激发试验诱导的GM-CSF和IL-5黏膜分泌。这些数据表明,GM-CSF和IL-5在鼻过敏原激发试验的无症状晚期反应中被诱导,并且单次剂量布地奈德预处理可预防这种细胞因子反应。