Soluble interleukin-4 receptor (sIL-4R) in allergic diseases

The mediator interleukin-4 (IL-4) plays an important role in the development of allergic inflammatory responses. IL-4 controls the production of IgE, expands IL-4 producing T cell subsets and stabilises effector cells functions. Based on this concept, it was aimed to neutralize secreted IL-4 molecules using recombinant soluble IL-4 receptors. The molecular characterization of soluble IL-4 receptors allowed the design of a recombinant drug initially evaluated in cell culture, then in animal models, followed by investigations of T cell functions from allergic patients in vitro. Based on these data, phase I/II studies have been initiated to take this approach from bench to bedside. Initial data reveal that this approach is safe and without drug-related toxicity. Stabilization of lung functions in moderate asthma patients has been reported. These results have proven the concept for a central role of IL-4 in the immunopathogenesis of allergic diseases. The immediate future will reveal whether neutralization of IL-4 with suitable drugs will provide an additional tool in the management of allergic patients.