Interleukin 5

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Interleukin 5 (IL-5) is an interleukin produced by type-2 T helper cells and mast cells.


Through binding to the interleukin-5 receptor, interleukin 5 stimulates B cell growth and increases immunoglobulin secretion—primarily IgA. It is also a key mediator in eosinophil activation.


IL-5 is a 115-amino acid (in human, 133 in the mouse) -long Th2 cytokine that is part of the hematopoietic family. Unlike other members of this cytokine family (namely interleukin 3 and GM-CSF), this glycoprotein in its active form is a homodimer.[1]

Tissue expression

The IL-5 gene is located on chromosome 11 in the mouse, and chromosome 5 in humans, in close proximity to the genes encoding IL-3, IL-4, and granulocyte-macrophage colony-stimulating factor (GM-CSF),[2][3] which are often co-expressed in Th2 cells. IL-5 is also expressed by eosinophils[4] and has been observed in the mast cells of asthmatic airways by immunohistochemistry.[5] IL-5 expression is regulated by several transcription factors including GATA3.[6]

Effect on eosinophils

Eosinophils are terminally differentiated granulocytes found in most mammals. The principal role of these cells, in a healthy host, is the elimination of antibody bound parasites through the release of cytotoxic granule proteins.[7] Given that eosinophils are the primary IL-5Rα-expressing cells, it is not surprising that this cell type responds to IL-5. In fact, IL-5 was originally discovered as an eosinophil colony-stimulating factor,[8] is a major regulator of eosinophil accumulation in tissues, and can modulate eosinophil behavior at every stage from maturation to survival. Mepolizumab is a monoclonal antibody antagonist IL-5 which can reduce excessive eosinophilia.

In Hodgkin lymphoma, the typically-observed eosinophilia is thought to be attributable to an increased production of IL-5.[9]


IL-5 has been shown to interact with interleukin 5 receptor alpha subunit.[10][11][12]


The IL-5 receptor is composed of an α and a βc chain.[13] The α subunit is specific for the IL-5 molecule, whereas the βc subunit also recognised by interleukin 3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF).[13][14] Glycosylation of the Asn196 residue of the Rα subunit appears to be essential for binding of IL-5.[15]

Clinical significance

Inhibitor of the IL-5 pathway.[16]

IL-5 has long been associated with the cause of several allergic diseases including allergic rhinitis and asthma, wherein a large increase in the number of circulating, airway tissue, and induced sputum eosinophils have been observed.[17]

Given the high concordance of eosinophils and, in particular, allergic asthma pathology, it has been widely speculated that eosinophils have an important role in the pathology of this disease.[18]

As of 2019, there are two FDA-approved monoclonal antibodies that inhibit IL-5, mepolizumab and reslizumab. Additionally, the antibody benralizumab blocks the interleukin-5 receptor. All three drugs are used to treat severe eosinophilic asthma[19] and eosinophilic granulomatosis with polyangiitis (EGPA).[20]

Another antibody, GSK3511294, is under development.[21]

Some hydroxyethylaminomethylbenzimidazole analogs have shown IL-5 inhibition in vitro.[22]


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  2. Lee JS, Campbell HD, Kozak CA, Young IG (March 1989). "The IL-4 and IL-5 genes are closely linked and are part of a cytokine gene cluster on mouse chromosome 11". Somatic Cell and Molecular Genetics. 15 (2): 143–152. doi:10.1007/BF01535075. PMID 2784591. S2CID 41719900. Archived from the original on 2023-10-10. Retrieved 2024-01-28.
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  15. Ishino T, Economou NJ, McFadden K, Zaks-Zilberman M, Jost M, Baxter S, et al. (September 2011). "A protein engineering approach differentiates the functional importance of carbohydrate moieties of interleukin-5 receptor α". Biochemistry. 50 (35): 7546–7556. doi:10.1021/bi2009135. PMID 21770429.
  16. Massey, Oliver William; Suphioglu, Cenk (January 2022). "Taking a Breather: Advances in Interleukin 5 Inhibition for Asthma Relief". International Journal of Molecular Sciences. 23 (19): 11166. doi:10.3390/ijms231911166. ISSN 1422-0067.
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External links

  • Overview of all the structural information available in the PDB for UniProt: P05113 (Interleukin-5) at the PDBe-KB.