Chung K F
Dept of Thoracic Medicine, National Heart & Lung Institute, Royal Brompton National Heart & Lung Hospital, London, UK.
Eur Respir J. 1995 Jul;8(7):1203-13. doi: 10.1183/09031936.95.08071203.
Cysteinyl leukotrienes are potent bronchoconstrictors, inducers of airway microvascular leakage and oedema, and of mucus secretion, in addition to causing an eosinophilic airway infiltration. Increased urinary excretion of the cysteinyl leukotriene E4 (LTE4) has been demonstrated following allergen challenge and during acute asthma attacks. Strategies for inhibition of cysteinyl leukotriene effects include antagonism of cysteinyl leukotriene receptors and inhibition of 5-lipoxygenase activity. In experimental challenge studies in asthmatic patients, these compounds can inhibit bronchoconstriction in response to exercise, aspirin and allergen. Results from clinical studies using receptor antagonists, such as ICI 204,219 and MK-571, and synthesis inhibitors, such as zileuton, demonstrate beneficial effects, with improvement in symptoms and forced expiratory volume in one second (FEV1), and a reduction in the use of beta 2-adrenergic relief medication. Further studies are needed to clarify the exact mechanisms by which these compounds provide beneficial effects. Cysteinyl leukotrienes are important mediators of asthma, and inhibition of their effects may represent a potential breakthrough in the therapy of asthma.
半胱氨酰白三烯是强效支气管收缩剂，可诱导气道微血管渗漏、水肿及黏液分泌，此外还会引起嗜酸性粒细胞气道浸润。变应原激发后及急性哮喘发作期间，已证实半胱氨酰白三烯E4（LTE4）的尿排泄量增加。抑制半胱氨酰白三烯作用的策略包括拮抗半胱氨酰白三烯受体及抑制5-脂氧合酶活性。在哮喘患者的实验激发研究中，这些化合物可抑制运动、阿司匹林及变应原引起的支气管收缩。使用受体拮抗剂（如ICI 204,219和MK-571）及合成抑制剂（如齐留通）的临床研究结果显示出有益效果，症状改善，一秒用力呼气量（FEV1）增加，且β2-肾上腺素能缓解药物的使用减少。需要进一步研究以阐明这些化合物产生有益效果的确切机制。半胱氨酰白三烯是哮喘的重要介质，抑制其作用可能代表哮喘治疗的潜在突破。
