The concept that airway inflammation leads to airway disease hasled to a widening search for the types of inflammatory cells and mediators that might be responsible for abnormal airway function. It has not yet been possible to integrate all of this information into a single model for the development of airway inflammation and remodeling, but a useful framework has been based on the behavior of the adaptive immune system. In that paradigm, an exaggeration of T helper type 2 (Th2) over Th1 responsesto allergic and nonallergic stimuli leads to airway inflammatory disease, especially asthma. In this review, we summarize alternative evidence that the innate immune system, typified by actions of airway epithelial cells and macrophages, may also be specially programmed for antiviral defense and abnormally programmed in inflammatory disease. In that regard, we concentrate on recent studies of specific IL-12 family members as a productof airway epithelial cells and a mediator of macrophage function. We also introduce evidence that abnormalities in epithelial programming may be inducible by paramyxoviral infection and, with the proper genetic background, may persist indefinitely. Taken together, we propose a new model that highlights specific interactions between epithelial, viral, and allergic(Epi-Vir-All) components and so better explains the basis for airway immunity, inflammation, and remodeling in response to viral infection and the development. Walter and Holtzman536 of long-term disease phenotypes typical of asthma and other hypersecretory airway diseases.
|Title of host publication||Therapeutic Targets in Airway Inflammation|
|Number of pages||28|
|State||Published - Jan 1 2003|