Th2 cytokines and asthma. Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists.
Interleukin-4 (IL-4) mediates important pro-inflammatory functions in asthma including induction of the IgE isotype switch, expression of vascular cell adhesion molecule-1 (VCAM-1), promotion of eosinophil transmigration across endothelium, mucus secretion, and differentiation of T helper type 2 lymphocytes leading to cytokine release. Asthma is a complex genetic disorder that has been linked to polymorphisms in the IL-4 gene promoter and proteins involved in IL-4 signaling. Soluble recombinant IL-4 receptor lacks transmembrane and cytoplasmic activating domains and can therefore sequester IL-4 without mediating cellular activation. We report the results of initial clinical trials, which demonstrate clinical efficacy of this naturally occurring IL-4 antagonist as a therapeutic agent in asthma.
Steinke
J W
JW
University of Virginia, Charlottesville, Virginia, USA.
Borish
L
L
D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000628:therapy*; D006801:Humans; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology*; D019948:Receptors, Interleukin-4 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000627:therapeutic use; D018418:Th2 Cells / Q000276:immunology*
D019948:Receptors, Interleukin-4; D011994:Recombinant Proteins; D015847:Interleukin-4