Molecular and clinical rationale for therapeutic targeting of interleukin-5 and its receptor

Clin Exp Allergy. 2012 May;42(5):712-37. doi: 10.1111/j.1365-2222.2011.03854.x. Epub 2011 Sep 23.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Allergic Agents / adverse effects
  • Anti-Allergic Agents / therapeutic use
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use
  • Disease Models, Animal
  • Eosinophils / immunology*
  • Humans
  • Hypersensitivity / drug therapy*
  • Hypersensitivity / immunology*
  • Interleukin-5 / antagonists & inhibitors*
  • Interleukin-5 / metabolism
  • Protein Binding
  • Receptors, Interleukin-5 / antagonists & inhibitors*
  • Receptors, Interleukin-5 / metabolism
  • Signal Transduction


  • Anti-Allergic Agents
  • Antibodies, Monoclonal
  • Interleukin-5
  • Receptors, Interleukin-5