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.
Devos
R
R
Roche Research Gent, Belgium.
Plaetinck
G
G
Cornelis
S
S
Guisez
Y
Y
Van der Heyden
J
J
Tavernier
J
J
D000818:Animals; D002908:Chronic Disease; D004802:Eosinophilia / Q000188:drug therapy*; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy*; D015848:Interleukin-5 / Q000037:antagonists & inhibitors*; D018123:Receptors, Interleukin / Q000032:analysis / Q000037:antagonists & inhibitors*; D053649:Receptors, Interleukin-5
D015848:Interleukin-5; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5