ABSTRACT

Conceptually, we envision two major pathways by which the airway nervous system may participate in airway inflammation and, as a consequence of in­ flammation, remodeling. One hypothesis is that neural pathways could play a key initiating role in the airway inflammatory cascade that leads to remodel­ ing. An alternate hypothesis is that airway inflammation, initiated by other means, induces changes in the behavior of airway nerves and/or receptors for products released by nerves that could contribute to the persistence (chronicity) of airway inflammation and thereby amplify the remodeling process. For the purposes of our discussion, we define remodeling as structural changes in the airways that result in measurable increases in the thickness of the airway, an alteration in the extracellular matrix components of the wall, and both hy­ perplasia and hypertrophy of resident cells such as smooth muscle cells (1). This is an active process and involves cell growth, cell death, cell migration,

Figure 1 Diagrammatic demonstration of multiple potential sites of interactions be­ tween neurons and other cells leading to inflammation/remodeling in the airways. NK1, neurokinen 1 receptor; SP, substance P; IL-8, interleuken 8; LIF, leukemia inhibitory factor; DRG, dorsal root ganglion; LTD4, leukotriene D4.