Immunologic basis of antigen-induced airway hyperresponsiveness.

The incidence, morbidity, and mortality of asthma has increased worldwide over the last two decades. Asthma is a complex inflammatory disease of the lung characterized by variable airflow obstruction, airway hyperresponsiveness (AHR), and airway inflammation. The inflammatory response in the asthmatic lung is characterized by infiltration of the airway wall with mast cells, lymphocytes, and eosinophils. Although asthma is multifactorial in origin, the inflammatory process in the most common form of the disease (extrinsic asthma) is believed to be a result of inappropriate immune responses to common aero-allergens in genetically susceptible individuals. As such, it has been hypothesized that CD4+ T cells that produce a Th2 pattern of cytokines play a pivotal role in the pathogenesis of this disease. Through the release of cytokines such as IL-4, IL-13, and IL-5, these cells orchestrate the recruitment and activation of the primary effector cells of the allergic response, the mast cell and the eosinophil. Activation of these cells results in the release of a plethora of inflammatory mediators that individually or in concert induce changes in airway wall geometry and produce the symptoms of the disease. The aim of this review is to discuss our current understanding of the pathophysiologic mechanisms by which Th2 cytokines induce airway disease, and the factors that predispose to the generation of these pathogenic cells in response to inhalation of ubiquitous aero-allergens. Elucidation of the exact immunological basis for allergic asthma may yield immunotherapeutic strategies to reverse the development of pathogenic Th2-mediated immune responses and reduce the morbidity and mortality associated with this disease.