Effects of inhaled aminophylline on airway constriction and inflammation in ovalbumin-sensitized guinea pigs
Effects of inhaled aminophylline on airway constriction and inflammation in ovalbumin-sensitized guinea pigs
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DOI：
10.3109/10717544.2013.846434
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发表时间：
2014-07
期刊：
影响因子：
6
通讯作者：
M. Muraki;Shota Wada;Takeshi Ohno;Souichirou Hanada;H. Sawaguchi;T. Iwanaga;H. Kume;Y. Tohda
中科院分区：
文献类型：
--
作者：
M. Muraki;Shota Wada;Takeshi Ohno;Souichirou Hanada;H. Sawaguchi;T. Iwanaga;H. Kume;Y. Tohda
摘要背景：茶碱的全身给药对哮喘的治疗是有用的。然而，其狭窄的治疗范围使其难以使用。关于其在吸入治疗中的潜力，特别是重复吸入，知之甚少。目的：探讨吸入氨茶碱对哮喘的治疗作用。研究方法：采用卵白蛋白（OVA）致敏豚鼠，评价吸入氨茶碱（25 mg/mL，30 min/剂）预处理对卵白蛋白（OVA）激发后气道反应和炎症以及气道对乙酰胆碱（Ach）超敏反应的影响。结果：氨茶碱呈浓度依赖性地舒张乙酰胆碱引起的离体气管平滑肌收缩。单剂量吸入氨茶碱预处理抑制OVA诱导的气道收缩的程度与腹腔注射高剂量氨茶碱（10-20 mg/kg）预处理相同。然而，单剂量氨茶碱吸入预处理不能抑制嗜酸性粒细胞浸润到气道（无论是支气管肺泡灌洗液[BAL]液，也没有肺组织），并没有抑制气道高反应性ACh，24小时后，OVA的挑战。重复吸入氨茶碱（每天两次，持续7天）抑制嗜酸性粒细胞的浸润和抑制气道过敏ACh。此外，高浓度的氨茶碱抑制BAL细胞产生的氧自由基。结论：单剂量吸入氨茶碱治疗具有短暂但相对较强的支气管扩张作用，这是由于将高剂量递送到局部气道中。反复吸入治疗可抑制过敏原诱导的气道炎症和超敏反应。因此，吸入氨茶碱可能对哮喘治疗有用。
Abstract Background: The systemic administration of theophylline is useful for asthma treatment. However its narrow therapeutic range makes it difficult to use. Little is known about its potential in inhalation therapy, particularly repeated inhalation. Objective: The purpose of this study is to investigate the therapeutic usefulness of inhaled aminophylline in an asthma model. Methods: The effects of pretreatment with inhaled aminophylline (25 mg/mL for 30 min/dose) on airway response and inflammation after an ovalbumin (OVA) challenge and airway hypersensitivity to acetylcholine (Ach) were evaluated using guinea pigs sensitized with OVA. Results: Aminophylline relaxed the ACh-induced contraction of tracheal smooth muscle in vitro in a concentration-dependent manner. Pretreatment with single-dose aminophylline inhalation suppressed OVA-induced airway constriction to the same extent as the intraperitoneal pretreatment with high-dose aminophylline (10–20 mg/kg). However, pretreatment with single-dose aminophylline inhalation did not suppress eosinophil infiltration into airways (neither bronchoalveolar lavage [BAL] fluid nor lung tissue) and did not suppress airway hyperreactivity to ACh, 24 h after OVA challenge. Repeated inhalation of aminophylline (twice daily for 7 days) suppressed the infiltration of eosinophils and suppressed airway hypersensitivity to ACh. In addition, high concentrations of aminophylline inhibited production of oxygen radicals by BAL cells. Conclusion: Single-dose inhalation treatment with aminophylline has transient but relatively strong bronchodilating effects due to delivery of high doses into local airways. Repeated inhalation treatment suppressed airway inflammation and hypersensitivity induced by allergens. Therefore, inhaled aminophylline may be useful for asthma treatment.