Modulation of airway sensitivity to inhaled irritants: Role of inflammatory mediators

Bronchopulmonary C-fiber endings and rapidly adapting pulmonary receptors ( RARs) are primarily responsible for eliciting the defense reflexes in prote cting the lungs against inhaled irritants. In anesthetized animals, inhalat ion of cigarette smoke, one of the common inhaled irritants, into the lungs elicits pulmonary chemoreflexes that are mediated through the stimulation of pulmonary C fibers. When the C-fiber conduction is selectively blocked i n the vagus nerves, the same smoke inhalation triggered only augmented brea ths, a reflex effect of activating RARs, in the same animals. Indeed, elect rophysiologic study shows that inhaled smoke exerts a direct stimulatory ef fect on both types of afferents. Increasing evidence indicates that the exc itability of these afferents and therefore their reflex actions are enhance d by airway mucosal inflammation; one such example is the airway hyperrespo nsiveness induced by acute exposure to ozone. Although the mechanism underl ying the inflammation-induced hypersensitivity of C-fiber endings is not fu lly understood, the possible involvement of local release of certain inflam matory mediators, such as histamine and prostaglandin E-2 (PGE(2)), should be considered. It is believed that changes in the membrane properties media ted by the activation of certain specific receptor proteins located on the membrane of these nerve terminals are involved, as the sensitizing effects of PGE2 can be also demonstrated in cultured pulmonary C neurons.