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Review
. 2001;2(2):66-70.
doi: 10.1186/rr40. Epub 2001 Feb 19.

Th2 cytokines and asthma. Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists

J W Steinke  1 , L Borish
Affiliations
Review

Th2 cytokines and asthma. Interleukin-4: its role in the pathogenesis of asthma, and targeting it for asthma treatment with interleukin-4 receptor antagonists

J W Steinke et al. Respir Res. 2001.

Abstract

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.

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Figures

Figure 1
Figure 1
IL-4 binding to cellular IL-4R and its inhibition by soluble IL-4R (sIL-4R). (a) IL-4 binds to cellular IL-4R, mediating cellular activation and important pro-inflammatory functions in asthma. For clarity, only the IL-4Rα chain of the heterodimer is shown, represented by three domains: extracellular (green), transmembrane (white) and cytoplasmic (red). It should be noted, however, that both chains of the heterodimer are required to initiate intracellular signaling. (b) The sIL-4R consists of the extracellular portion of IL-4Rα. It retains the ability to bind IL-4 with high affinity and high specificity and thereby functions as a decoy receptor which can sequester naturally occurring IL-4 and prevent it from activating the cell. sIL-4R cannot activate cellular signaling; thus, it serves as an anti-inflammatory agent that can counter the effects of IL-4 in asthma.
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