Banner K H, Page C P
Dept of Pharmacology, King's College, University of London, UK.
Eur Respir J. 1995 Jun;8(6):996-1000.
Theophylline has been in clinical use for the treatment of bronchial asthma and other respiratory diseases for well over 50 yrs. Over this time, a considerable body of evidence has accumulated to show that this drug has a wide range of pharmacological actions, in addition to the well-recognized action on airway smooth muscle function. Current evidence suggests that part of the therapeutic value of theophylline in the treatment of asthma is by virtue of an anti-inflammatory or immunomodulatory effect, although the actual mechanism of action remains unclear. It has been proposed that the observed anti-inflammatory effects of theophylline could be attributed to phosphodiesterase (PDE) inhibition, and recently the type III and IV isoenzymes have been characterized in a number of inflammatory cells. This article reviews the evidence that theophylline and the newer more selective type IV PDE isoenzyme inhibitors can inhibit the activation of inflammatory cell types, such as T-lymphocytes, eosinophils, mast cells and macrophages, in vitro. The evidence supporting the ability of theophylline and selective PDE IV isoenzyme inhibitors to modify allergic inflammation both in animal models and clinical asthma is also discussed. We conclude that theophylline possesses important anti-inflammatory and immunomodulatory activity and that, in light of this evidence, it is timely to reconsider the place of theophylline in the treatment of asthma.
茶碱已在临床用于治疗支气管哮喘和其他呼吸道疾病超过50年。在此期间，大量证据积累表明，除了对气道平滑肌功能的公认作用外，该药物还具有广泛的药理作用。目前的证据表明，茶碱在哮喘治疗中的部分治疗价值在于其抗炎或免疫调节作用，尽管其实际作用机制仍不清楚。有人提出，茶碱观察到的抗炎作用可能归因于磷酸二酯酶（PDE）抑制，最近III型和IV型同工酶已在多种炎症细胞中得到表征。本文综述了茶碱和更新的更具选择性的IV型PDE同工酶抑制剂在体外可抑制炎症细胞类型（如T淋巴细胞、嗜酸性粒细胞、肥大细胞和巨噬细胞）活化的证据。还讨论了支持茶碱和选择性PDE IV同工酶抑制剂在动物模型和临床哮喘中改变过敏性炎症能力的证据。我们得出结论，茶碱具有重要的抗炎和免疫调节活性，鉴于此证据，重新考虑茶碱在哮喘治疗中的地位是适时的。
