KININS IN THE PATHOGENESIS OF HUMAN AIRWAY DISEASES

1. Over the past decade, data have been obtained showing that the pote nt vasoactive peptides known as kinins are generated in airway secreti ons during a variety of inflammatory airway diseases, such as allergic rhinitis, viral rhinitis and asthma. Kinin generation involves releas e of tissue kallikrein from airway glands, as well as increased vascul ar permeability and activation of the plasma kallikrein system. The ac tivity 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 inflam mation. In the upper airways, kinins can stimulate glandular secretion , increase Vascular permeability and stimulate sensory nerves to produ ce symptoms of nasal obstruction, rhinorrhea, and nasal and throat irr itation. In the lower airways of asthmatics, kinins are potent inducer s 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 r eceptor antagonists that have been available to date have suffered fro m problems of potency or duration of action. Studies are continuing, h owever, to understand the mechanisms by which kinins exert their effec ts and to delineate their importance in airway diseases.