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Is platelet activating factor (PAF) an important mediator in bronchial asthma?
R H Gundel1, H O Heuer, L G Letts
1Department of Pharmacology Boehringer Ingelheim Pharmaceuticals Inc. Ridgefield CT 06877 USA.
Mediators of Inflammation
|January 1, 1992
Summary
Platelet-activating factor (PAF) receptor antagonists show limited efficacy for treating human asthma. Despite preclinical promise, recent primate and human studies indicate PAF may not be a key target for asthma therapy.
Area of Science:
- Immunology
- Pulmonology
- Pharmacology
Background:
- Platelet-activating factor (PAF) is implicated in asthma pathogenesis.
- PAF receptor antagonists have shown promise in preclinical asthma models.
- The relevance of acute inflammatory models to chronic human asthma is uncertain.
Purpose of the Study:
- To evaluate the efficacy of PAF receptor antagonists in chronic airway inflammation and hyperresponsiveness.
- To assess the therapeutic potential of PAF receptor antagonists in human asthma.
Main Methods:
- Testing PAF receptor antagonists in a primate model of chronic airway inflammation.
- Clinical studies involving human asthmatics treated with PAF receptor antagonists.
Main Results:
- PAF receptor antagonists did not reduce chronic inflammation or hyperresponsiveness in a primate asthma model.
- Human studies failed to demonstrate efficacy in blocking allergen responses or providing steroid-sparing effects.
Conclusions:
- PAF may not be a critical mediator for blocking in bronchial asthma therapy.
- Current PAF receptor antagonists are unlikely to provide a novel therapeutic approach for human asthma.
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