Animal models for testing anti-inflammatory drugs for treatment of bronchial hyperreactivity in asthma.
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.
Linssen
M J
MJ
Boehringer Mannheim GmbH, Allergy Department, FRG.
Wilhelms
O H
OH
Timmerman
H
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D006801:Humans
D000894:Anti-Inflammatory Agents, Non-Steroidal