INTERLEUKIN-5 AND ITS RECEPTOR - A DRUG TARGET FOR EOSINOPHILIA ASSOCIATED WITH CHRONIC ALLERGIC DISEASE

A characteristic feature of chronic allergic diseases such as asthma is the increase in eosinophil numbers in the inflamed tissue. In light of its specificity for the development of eosinophils, interleukin-5 (IL-5) is considered the most important cytokine involved in the regulation of eosinophilia. Hence, an antagonist for IL-5 activity is a new target for drug discovery programs, We have examined the opportunity for both a random and a rational approach for the identification of such an antagonist, The elucidation of the structure of IL-5 and the initial structure/function analysis of the ligand/receptor complex constitute a first step towards the design of antagonistic compounds, The identification of a small compound by random screening able to inhibit the IL-5/IL-5 receptor interaction indicated an important domain in the receptor, We examine here protein based IL-5 antagonists, such as IL-5-muteins, soluble IL-5 receptor constructs, and monoclonal antibodies, for their potential as IL-5/IL-5 receptor antagonists, and the use of a murine model of eosinophil airway inflammation for their evaluation.