IL-4- and IL-13-directed approaches

Interleukin 4 (IL-4) and IL-13 mediate important prointlammatory functions in asthma including Th2 lymphocyte differentiation, induction of IgE production, upregulation 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 and IL-13 in the pathogenesis of asthma is further supported by identification of polymorphisms linked to asthma in the IL-4 and IL-13 promoters, the genes themselves and proteins involved in signaling for the two cytokines. Several approaches to IL-4 antagonism arc or have been in clinical development. The focus of this chapter will be to examine IL-4 and IL-13, the antagonists that have been developed, discuss early trial results and speculate on what the future holds for anti-IL-4 or anti-IL-13 therapy.