Interleukin-5 is a Th2 homodimeric cytokine involved in the differentiation, 
maturation, migration, development, survival, trafficking and effector function 
of blood and local tissue eosinophils, in addition to basophils and mast cells. 
The IL-5 receptor (IL-5R) consists of an IL-5-specific α subunit that interacts 
in conformationally dynamic ways with the receptor's βc subunit, an aggregate of 
domains it shares with binding sites of IL-3 and granulocyte-macrophage 
colony-stimulating factor. IL-5 and IL-5R drive allergic and inflammatory immune 
responses characterizing numerous diseases, such as asthma, atopic dermatitis, 
chronic obstructive pulmonary disease, eosinophilic gastrointestinal diseases, 
hyper-eosinophilic syndrome, Churg-Strauss syndrome and eosinophilic nasal 
polyposis. Although corticosteroid therapy is the primary treatment for these 
diseases, a substantial number of patients exhibit incomplete responses and 
suffer side-effects. Two monoclonal antibodies have been designed to neutralize 
IL-5 (mepolizumab and reslizumab). Both antibodies have demonstrated the ability 
to reduce blood and tissue eosinophil counts. One additional monoclonal 
antibody, benralizumab (MEDI-563), has been developed to target IL-5R and 
attenuate eosinophilia through antibody-dependent cellular cytotoxicity. All 
three monoclonal antibodies are being clinically evaluated. Antisense 
oligonucleotide technology targeting the common βc IL-5R subunit is also being 
used therapeutically to inhibit IL-5-mediated effects (TPI ASM8). Small 
interfering RNA technology has also been used therapeutically to inhibit the 
expression of IL-5 in animal models. This review summarizes the structural 
interactions between IL-5 and IL-5R and the functional consequences of such 
interactions, and describes the pre-clinical and clinical evidence supporting 
IL-5R as a therapeutic target.