Kinins in the pathogenesis of human airway diseases

1. Over the past decade, data have been obtained showing that the potent vasoactive peptides known as kinins are generated in airway secretions during a variety of inflammatory airway diseases, such as allergic rhinitis, viral rhinitis and asthma. Kinin generation involves release of tissue kallikrein from airway glands, as well as increased vascular permeability and activation of the plasma kallikrein system. The activity of generated kinins is regulated by a number of cell-associated, as well as plasma-derived, peptidases. 2. Kinins can induce relevant symptoms when applied to the surface of human airways. Moreover, the effects of kinins are more pronounced in the setting of chronic inflammation. In the upper airways, kinins can stimulate glandular secretion, increase vascular permeability and stimulate sensory nerves to produce symptoms of nasal obstruction, rhinorrhea, and nasal and throat irritation. In the lower airways of asthmatics, kinins are potent inducers of edema and cause bronchoconstriction by a mechanism that involves, at least in part, neural reflexes. 3. Definitive proof of a role for kinins in human airway diseases has been difficult to obtain because receptor antagonists that have been available to date have suffered from problems of potency or duration of action. Studies are continuing, however, to understand the mechanisms by which kinins exert their effects and to delineate their importance in airway diseases.