The immunopharmacology of mild asthma.

If cell numbers, activation state, or mediators, for example, can be correlated with some clinical measure of disease severity, a major effector role in the disease may be postulated. Mast cells, along with eosinophils and lymphocytes, are present in increased numbers in the airways of patients with asthma. Mast cell mediators are also increased in persons with allergies, with the concentrations of histamine, tryptase, and prostaglandin D2 being proportional to the degree of airway obstruction and bronchial hyperresponsiveness. Increased numbers of activated must cells and eosinophils (but not T cells or macrophages) were also found in bronchoalveolar lavage fluid in children. The mast cell is also known to release a range of cytokines (e.g., tumor necrosis factor-alpha and IL-4) that have various important functions, including upregulation of the endothelial adhesion molecules that are responsible for eosinophil recruitment from the microvascular circulation into the airways and subsequent activation. Mast cell staining for secreted IL-4 was found to be proportional to the infiltration of eosinophils and lower airway symptoms in patients with seasonal asthma, which is compatible with the concept that mast cells alone can sustain a continuing allergic inflammatory response. The mast cell proteases chymase and tryptase are also important for eosinophil recruitment and activation and for increasing mucus secretion and microvascular permeability. The evidence that the human mast cell is capable of releasing proteases and cytokines that have the capacity to initiate and maintain a chronic inflammatory response provides a mechanism whereby the clinical efficacy of nedocromil sodium in patients with chronic mild to moderate asthma can be explained.