Mechanisms of inflammation and potential role in the pathogenesis of asthma

Neurogenic inflammation produces potent responses in multiple cells in the airways. These responses normally are limited by the presence on the surface of target cells of neutral endopeptidase (NEP), an enzyme that cleaves and inactivates neuropeptides that come in close contact with the cell and thereby limits neurogenic inflammatory responses. Inhibition of NEP by drugs, respiratory viruses, cigarette smoke, and toluene diisocyanate result in exaggerated neurogenic responses, while upregulation of NEP (e.g., by corticosteroids) may suppress the responses. Exogenously delivered recombinant human NEP also inhibits the responses. The novel system whereby sensory nerve stimulation results in the release of inflammatory neuropeptides provides a potentially important mechanism in the pathogenesis of airway inflammation. The strategies discussed here provide tools for the investigation of this system and suggests methods for therapeutic intervention.