IL-13 as a therapeutic target for respiratory disease.
Interleukin-13 (IL-13) is a critical mediator of asthma pathology. On B cells, monocytes, epithelial cells, and smooth muscle cells, IL-13 acts through the IL-13Ralpha1/IL-4Ralpha complex to directly induce activation responses that contribute to atopic disease. In human populations, genetic polymorphisms in IL-13, its receptor components, or the essential signaling element STAT6, have all been associated with increased risk of atopy and asthma. Animal studies using IL-13 deficient mice, IL-13 transgenic animals, and IL-13 neutralization strategies have confirmed an essential role for this cytokine in driving major correlates of asthma pathology, including airway hyperresponsiveness (AHR), lung eosinophilia, mucus generation, and fibrosis. Ongoing studies continue to define both overlapping and distinct roles for IL-13 and the related cytokine, IL-4, in promoting asthmatic changes. Furthermore, new evidence concerning the role of the "decoy" receptor, IL-13Ralpha2, has prompted re-evaluation of the receptor forms that underlie the numerous activities of IL-13. In this review, we summarize the essential role of IL-13 in asthma, compare the relative contributions of IL-13 and IL-4 to key aspects of the asthmatic phenotype, and outline novel therapeutic strategies to target this critical cytokine.
Kasaian
Marion T
MT
Department of Discovery Inflammation, Wyeth Research, 200 CambridgePark Drive, Cambridge, MA 02140, USA. mkasaian@wyeth.com
Miller
Douglas K
DK
D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology; D005355:Fibrosis / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D009093:Mucus / Q000276:immunology; D011110:Polymorphism, Genetic; D053660:Receptors, Interleukin-13 / Q000276:immunology; D019948:Receptors, Interleukin-4 / Q000276:immunology
D018793:Interleukin-13; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4