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Interleukin‐5 and its receptor: a drug target for eosinophilia associated with chronic allergic disease
Author(s) -
Devos René,
Plaetinck Geert,
Comelis Sigrid,
Guisez Yves,
Van der Heyden José,
Tavemier Jan
Publication year - 1995
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.57.6.813
Subject(s) - biology , eosinophilia , immunology , interleukin 5 , interleukin 4 receptor , disease , interleukin 2 , drug , receptor , interleukin , eosinophil , interleukin 4 , cytokine , pharmacology , medicine , asthma , genetics
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. J . Leukoc. Biol. 57: 813–819; 1995.