Molecular and cellular mechanisms of allergic disease

The molecular and cellular mechanisms mediating the allergic inflammatory c ascade involve multiple mediators, cell types, and pathways. Of particular interest are the pathways regulated by the T(H)2 lymphocyte, which result i n release of IL-4 (important to IgE synthesis) and IL-5 (important to eosin ophil proliferation). IL-4 regulates differentiation of naive THO cells to develop a T(H)2 phenotype and stimulates B cells to produce IgE. Cross-link ing by allergen of IgE affixed to high-affinity receptors on mast cells and basophils triggers degranulation and the release of preformed inflammatory mediators (important to the early phase response), and subsequently initia tes synthesis and the release of lipid mediators and cytokines (which may c ontribute to the late phase response). Eosinophils may also play a prominen t role in the development of bronchial hyperreactivity. IL-5, which is a li neage-specific eosinophil grow th factor, increases the formation of eosino phils from progenitor cells and, in concert with CCR3 active chemokines, in creases their trafficking to sites of allergic inflammation. An improved un derstanding of the basic mechanisms of allergic inflammation has led to the discovery of molecular targets involved in the initial events of the infla mmatory cascade. Potential targets for the development of novel therapies f or allergic disease include IgE, the T(H)2 lymphocyte, and T(H)2-derived cy tokines, IL-4 and IL-5.