Asthma is one of the most common chronic respiratory diseases in industrialized countries, and imposes high social and economic costs. It affects approximately 155 million individuals throughout the world and its reported incidence is increasing dramatically in many developed nations.1,2) Extensive studies on the pathogenetic mechanisms have clarified that asthma is characterized by abnormal accumulation and activation of immune-related cells in the airways, and by dysfunction of specialized parenchymal cells, 3) including eosinophils, as well as T cells, monocytes, and neutrophils. 4)Rather than being a single disease, asthma is currently considered to be a group of different disorders characterized by three major features: (1) intermittent and reversible airway obstruction leading to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing; (2) bronchohyperresponsiveness (BHR), which is defined as an increased sensitivity to broncho-constrictors such as histamine or cholinergic agonists; and (3) airway inflammation. 2)Studies on the mechanisms of asthma have been mainly focused on two areas: immunoglobulin E (IgE) and cytokines induced by Th cells. IgE is set apart from the other immunoglobulin isotypes by its very low plasma levels and short half-life. In addition to triggering immediate-hypersensitivity reactions and late-phase responses, there is accumulating evidence that preformed IgE can augment humoral and cellular immune responses to allergens. 5) IgE is believed to be one of the major mediators of the immediate hypersensitivity reactions that underlie atopic conditions such as urticaria, seasonal allergy, asthma and anaphylaxis.6) IgE blockers have recently been developed and show some promise for the treatment of allergic diseases. 7,8) The strong association of IgE with atopic diseases, and its documented role in immediate hypersensitivity reactions in the airway, have driven efforts to define the cellular and molecular interactions that regulate its production. Consequently, it has been established that the production of IgE is tightly regulated and involves a complex network of cellular and molecular signals.5) Immune responses to protein antigens are strongly influenced by the nature of the helper T lymphocyte (Th) subsets participating in the response. Th1 cells, through the production of IFN-g, have been shown to evoke cell-dependent immunity and to inhibit the production of IL-4 by Th2 cells, as well as Th2 cell proliferation in vitro.9,10) Th1 cells also promote immunoglobulin class switching to IgG2a. 4) In mice, the Th1 cytokine IFN-g has inhibitory effects on Th2-induced airway eosinophilia and airway hyper-responsiveness (AHR).11) In contrast, IL-4, secreted by Th2 cells, is the exclusive IgE isotype switching factor; it is responsible for the over-production of IgE, it can promote immunoglobulin class switching to IgG1 and IgE,4) and it stimulates IgE gene recombination and transcription to IgE mRNA, thereby enhancing IgE production by B cells. 12,13) It is now well ...
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