Molecular mechanisms of atopy.

Production of specific immunoglobulin (Ig)E is the characteristic abnormality of atopy. IgE is produced by B lymphocytes under the influence of interleukin (IL)4 and IL-13. IgE binds to high-affinity IgE receptors (Fc«RI) on mast cells to induce degranulation and mediator synthesis. IL-4 enhances the activation of Fc«RI to augment the production of cytokines and lipid mediators. These receptors may also be expressed on other cells such as basophils, monocytes and eosinophils. IgE may also activate low-affinity IgE receptors (Fc«RII or CD23) that are expressed on B lymphocytes, T lymphocytes, macrophages and airway smooth muscle cells. CD23 expression is enhanced by IL-4. Recently, a humanised murine monoclonal antibody (E25) directed against IgE has demonstrated a reduction in early and late responses to inhaled allergen and eosinophil counts in induced sputum, and reduced airway hyperresponsiveness. There is a profound reduction in circulating IgE, which may be due to switching-off IgE production from B cells. In patients with severe asthma who require oral steroids there is a significant reduction in oral steroid requirements, and several patients are able to completely withdraw oral steroids in comparison with a placebo. E25 may also reduce signalling through CD23 as IgE levels are lowered and this might explain its efficacy in chronic asthma, through an inhibitory effect on T lymphocytes, macrophages, eosinophils and airway smooth muscle.