Th2-type cytokines such as IL-4, IL-5, and IL-13 orchestrate a cascade of events during development of an allergic inflammatory response. This is demonstrated both clinically and in preclinical animal models (404, 405). IL-4 plays a critical role in the early commitment of ThO cells to Th2 cells and regulates IgE secretion by B-cells. It also induces V-CAM expression on endothelial cells, promotes eosinophilic inflammation, and increases airway mucus production.
In asthmatic patients there is an increase in serum and bronchoalveolar lavage fluid IL-4 levels, and atopic individuals have a higher frequency of IL-4-producing T-cells (406, 407). Genetic studies have linked asthma and atopy to the chromosome region 5q31-33, which includes IL-4, IL-5, IL-9, and the IL-13 genes (408). Thus, aberrant production of IL-4, or excessive response to this cytokine resulting from genetic defects, might contribute to the pathogenesis of asthma.
IL-4 is a 20-kDa secreted glycoprotein and its expression is highly tissue specific. IL-4 is produced by Th2 cells and natural killer cells in response to stimulation through the T-cell receptor (409). IL-4 binds to two types of receptor complexes, type I and type II receptors. Type I receptor complexes are formed by the IL-4 receptor a chain (IL-4Ro:) and the common y chain (yC), whichform part of the many other cytokine receptor complexes. The type II receptor consists of the IL-4Ra chain and the IL-13R« chain. In both cases signaling occurs through the JAK/STAT pathway, more specifically through activation of STAT6 (410).
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If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.