Nyce J W, Metzger W J
Department of Molecular Pharmacology and Therapeutics, EpiGenesis Pharmaceuticals, Greenville, North Carolina 27834, USA.
Nature. 1997 Feb 20;385(6618):721-5. doi: 10.1038/385721a0.
Asthma is an inflammatory disease characterized by bronchial hyper-responsiveness that can proceed to life-threatening airway obstruction. It is one of the most common diseases in industrialized countries, and in the United States accounts for about 1% of all healthcare costs. Asthma prevalence and mortality have increased dramatically over the past decade, and occupational asthma is predicted to be the pre-eminent occupational lung disease in the next decade. Increasing evidence suggests that adenosine, an endogenous purine that is involved in normal physiological processes, may be an important mediator of bronchial asthma. In contrast to normal individuals, asthmatic individuals respond to adenosine challenge with marked airway obstruction, and concentrations of adenosine are elevated in the bronchoalveolar lavage fluid of asthma patients. We performed a randomized crossover study using the dust mite-conditioned allergic rabbit model of human asthma. Administration of an aerosolized phosphorothioate antisense oligodeoxynucleotide targeting the adenosine A1 receptor desensitized the animals to subsequent challenge with either adenosine or dust-mite allergen.
哮喘是一种炎症性疾病，其特征为支气管高反应性，可发展为危及生命的气道阻塞。它是工业化国家最常见的疾病之一，在美国约占所有医疗费用的1%。在过去十年中，哮喘的患病率和死亡率急剧上升，预计职业性哮喘将成为未来十年最主要的职业性肺病。越来越多的证据表明，腺苷作为一种参与正常生理过程的内源性嘌呤，可能是支气管哮喘的重要介质。与正常个体不同，哮喘患者对腺苷激发试验会出现明显的气道阻塞反应，且哮喘患者支气管肺泡灌洗液中的腺苷浓度升高。我们使用人类哮喘的尘螨致敏兔模型进行了一项随机交叉研究。给予雾化的硫代磷酸酯反义寡脱氧核苷酸靶向腺苷A1受体，可使动物对随后的腺苷或尘螨过敏原激发产生脱敏作用。
