Linssen M J, Wilhelms O H, Timmerman H
Boehringer Mannheim GmbH, Allergy Department, FRG.
Pharm Weekbl Sci. 1991 Dec 13;13(6):225-37. doi: 10.1007/BF02015576.
In the first part of this review the important role played by the bronchial hyperreactivity caused by chronic bronchopulmonary inflammation in asthma is described. Deliberately, more emphasis is placed on the role of pro-inflammatory eosinophils, alveolar macrophages, lymphocytes and platelets rather than on mast cells and neutrophils or the numerous mediators. The reason for this is that, on account of the large number of mediators and their multitude of functions and interactions in asthma, antagonism of a specific mediator will probably not be clinically relevant for optimally effective curative treatment of asthma. Inhibition of the infiltration and activation of pro-inflammatory cells is likely to be a more successful approach. In the second part, various animal models of bronchial hyperreactivity, which could be suitable for testing anti-asthmatic drugs, are discussed. Most animal models pay too little attention to chronic bronchopulmonary inflammation as the cause of bronchial hyperreactivity in asthma. In various models the bronchial hyperreactivity is provoked by a single mediator and this leads to selection of specific antagonists which are unlikely to be of clinical benefit. Rats appear to have certain advantages over guinea-pigs as experimental animals for bronchial hyperreactivity.
在本综述的第一部分,描述了慢性支气管肺炎症引起的支气管高反应性在哮喘中所起的重要作用。特意地,更多的重点放在促炎性嗜酸性粒细胞、肺泡巨噬细胞、淋巴细胞和血小板的作用上,而不是肥大细胞、中性粒细胞或众多介质的作用上。这样做的原因是,由于哮喘中介质数量众多及其多种功能和相互作用,针对特定介质的拮抗作用可能在临床上与哮喘的最佳有效治疗无关。抑制促炎性细胞的浸润和激活可能是一种更成功的方法。在第二部分中,讨论了各种可能适用于测试抗哮喘药物的支气管高反应性动物模型。大多数动物模型对作为哮喘中支气管高反应性原因的慢性支气管肺炎症关注太少。在各种模型中,支气管高反应性由单一介质诱发,这导致选择不太可能具有临床益处的特定拮抗剂。作为支气管高反应性实验动物,大鼠似乎比豚鼠具有某些优势。