Interleukin-13 (IL-13) is a monomeric 17 kDa immunoregulatory cytokine that plays a key role in the pathogenesis of allergy, cancer, and tissue fibrosis. It is secreted by several helper T cell subsets, NK cells, mast cells, eosinophils, basophils, and visceral smooth muscle cells (1?3). Mature human IL-13 shares approximately 58%?amino acid sequence identity with mouse and rat IL-13. Despite the low homology, it exhibits cross?species activity between human, mouse, and rat (4). IL-13 suppresses the production of proinflammatory cytokines and other cytotoxic substances by macrophages, fibroblasts, and endothelial cells. On B cells, it promotes cellular activation, immunoglobulin class switching to IgE, and the up?regulation of CD23/Fc epsilon RII (1,?5). IL-13 binds with low affinity to the transmembrane IL-13 R alpha 1 which then forms a signaling complex with the transmembrane IL-4 R alpha (6?8). This high affinity receptor complex also functions as the type 2 IL-4 receptor (6,?7). IL?13?R alpha 2 inhibits responses to both IL-13 and IL-4. It binds IL-13 with high affinity (9, 10) and prevents IL-13 from signaling through the IL-13 R alpha 1/IL-4 R alpha complex (11,?12). It also blocks signaling through IL-4-occupied IL-13 R alpha 1/IL-4 R alpha receptor complexes (12, 13). In addition, IL-13-bound IL-13 R alpha 2 can directly promote tumor cell invasiveness and the development of tissue fibrosis (14?16).
