Anti-interleukin-4 therapy.
Interleukin 4 (IL-4) mediates important pro-inflammatory functions in asthma, including T helper cell type 2 lymphocyte differentiation, induction of IgE production, up-regulation of IgE receptors, expression of vascular cell-adhesion molecule 1, promotion of eosinophil transmigration into the lungs, inhibition of T-lymphocyte apoptosis, and mucus hypersecretion. The role of IL-4 in the pathogenesis of asthma is supported by identification of polymorphisms linked to asthma in the IL-4 gene promoter and proteins involved in IL-4 signaling. Several approaches to IL-4 antagonism are or have been in clinical development. This article examines IL-4 and the antagonists that have been developed. Early trial results and the future of anti-IL-4 therapy are discussed.
Steinke
John W
JW
Asthma and Allergic Diseases Center, Bierne Carter Center for Immunology, University of Virginia Health System, Lane Road, MR4 Building, Room 5031, Box 801355, Charlottesville, VA 22908-1355, USA. js3ch@virginia.edu
D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D019948:Receptors, Interleukin-4 / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D015847:Interleukin-4