Spina D, Landells L J, Page C P
The Sackler Institute of Pulmonary Pharmacology, The Department of Respiratory Medicine, Kings College School of Medicine and Dentistry, London, UK.
Clin Exp Allergy. 1998 Aug;28 Suppl 3:24-34.
Theophylline has been used for over a century in the treatment of asthma and while it is used principally as a bronchodilator, a number of recent studies have demonstrated potential anti-inflammatory and immunomodulatory activity. Indeed, regular treatment with low-dose theophylline, affords significant clinical benefit at the expense of unwanted side-effects associated with this drug, including headache and vomiting. The mechanism of action of theophylline is unclear, although a significant body of evidence points to an involvement of phosphodiesterase enzyme inhibition. Phosphodiesterases are a diverse group of enzymes that belong to at least seven families and of particular interest is the role of phosphodiesterase 4 isoenzyme as it is distributed in a number of inflammatory and immune cells and whose inhibition results in the downregulation of inflammatory and immune cell function. The discovery of pharmacological drugs selective for this isoenzyme has been viewed with interest in light of the positive results from preclinical and early clinical studies. Whether orally active safe phosphodiesterase 4 isoenzyme inhibitors will be useful in the treatment of asthma remains to be established.
茶碱已用于治疗哮喘达一个多世纪之久，虽然它主要用作支气管扩张剂，但最近的一些研究表明它具有潜在的抗炎和免疫调节活性。事实上，低剂量茶碱的常规治疗虽能带来显著的临床益处，但却伴随着该药物的不良副作用，包括头痛和呕吐。尽管大量证据表明茶碱的作用机制涉及磷酸二酯酶抑制，但具体机制仍不清楚。磷酸二酯酶是一组多样的酶，至少属于七个家族，其中磷酸二酯酶4同工酶的作用尤为引人关注，因为它分布于多种炎症和免疫细胞中，抑制该同工酶会导致炎症和免疫细胞功能下调。鉴于临床前和早期临床研究的积极结果，人们对选择性作用于该同工酶的药理药物的发现颇感兴趣。口服活性安全的磷酸二酯酶4同工酶抑制剂是否对哮喘治疗有用仍有待确定。
