Asthma: an inflammatory mediator soup

Reversible or partially reversible airway obstruction, inflammation, and br onchial hyperresponsiveness to various stimuli are the defining characteris tics of asthma. Airway obstruction in asthma is a complex event that is due to bronchospasm, inflammation, and mucus formation. Inflammation has assum ed a more central role in the pathogenesis of the disease, as it contribute s not only to airflow obstruction, but also to bronchial hyperresponsivenes s. The inciting trigger, or inhaled allergen, in asthma induces the activat ion of mast cells and macrophages with the subsequent release of several pr oinflammatory mediators, including leukotrienes, chemotactic factors, and c ytokines. Antigen processed by macrophages is presented to undifferentiated T helper cells, inducing differentiation to the Th2 phenotype, with the su bsequent release of IL-4 and IL-5, causing IgE synthesis and eosinophil inf iltration, respectively. Macrophage-derived cytokines, such as IL-1, TNF-al pha, and IFN-gamma, activate endothelial cells, upregulating the expression of adhesion molecules such as ICAM-1 and VCAM-1, which permit egression of leukocytes from the vasculature to the airway mucosa. Several inflammatory cells, such as eosinophils, mast cells, and macrophages, not only cause ai rway damage, but also synthesize cytokines that perpetuate the inflammatory process. This complex interplay of inflammatory cells and mediators causes the classic histopathophysiologic features in the airways of both symptoma tic and asymptomatic individuals with asthma, emphasizing the importance of early recognition and antiinflammatory treatment.