Interleukin 5

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Interleukin 5
IL5 Crystal Structure.rsh.png
Crystal structure of human IL-5
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols IL5 ; EDF; IL-5; TRF
External IDs OMIM147850 MGI96557 HomoloGene679 ChEMBL: 1169600 GeneCards: IL5 Gene
RNA expression pattern
PBB GE IL5 207952 at tn.png
More reference expression data
Species Human Mouse
Entrez 3567 16191
Ensembl ENSG00000113525 ENSMUSG00000036117
UniProt P05113 P04401
RefSeq (mRNA) NM_000879 NM_010558
RefSeq (protein) NP_000870 NP_034688
Location (UCSC) Chr 5:
131.88 – 131.89 Mb
Chr 11:
53.72 – 53.73 Mb
PubMed search [1] [2]

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


Through binding to the IL-5 receptor, IL-5 stimulates B cell growth and increases immunoglobulin secretion. 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 IL-3 and GM-CSF), this glycoprotein in its active form is a homodimer.[1]

Tissue expression[edit]

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. Interleukin-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]

Clinical significance[edit]

Interleukin-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.[7] 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.[8]

Effect of IL-5 on Eosinophils[edit]

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.[9] 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,[10] 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 against IL-5 which can reduce excessive eosinophilia.

In Hodgkin lymphoma, for instance, the typically-observed eosinophilia is thought to be attributable to an increased production of IL-5.[11]


Interleukin 5 has been shown to interact with Interleukin 5 receptor alpha subunit.[12][13][14]


The IL-5 receptor is composed of an α and a βc chain.[15] 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).[15][16] Glycosylation of the Asn196 residue of the Rα subunit appears to be essential for binding of IL-5.[17]


  1. ^ Milburn M, Hassell A, Lambert M, Jordan S, Proudfoot A, Graber P et al. (May 1993). "A novel dimer configuration revealed by the crystal structure at 2.4 A resolution of human interleukin-5". Nature 363 (6425): 172–6. doi:10.1038/363172a0. PMID 8483502. 
  2. ^ Lee J, Campbell H, Kozak C, Young I (March 1989). "The IL-4 and IL-5 genes are closely linked and are part of a cytokine gene cluster on mouse chromosome 11". Somat. Cell Mol. Genet. 15 (2): 143–52. doi:10.1007/BF01535075. PMID 2784591. 
  3. ^ van Leeuwen B, Martinson M, Webb G, Young I (April 1989). "Molecular organization of the cytokine gene cluster, involving the human IL-3, IL-4, IL-5, and GM-CSF genes, on human chromosome 5". Blood 73 (5): 1142–8. PMID 2564789. 
  4. ^ Dubucquoi S, Desreumaux P, Janin A, Klein O, Goldman M, Tavernier J et al. (February 1994). "Interleukin 5 synthesis by eosinophils: association with granules and immunoglobulin-dependent secretion". J. Exp. Med. 179 (2): 703–8. doi:10.1084/jem.179.2.703. PMC 2191391. PMID 8294877. 
  5. ^ Bradding P, Roberts J, Britten K, Montefort S, Djukanovic R, Mueller R et al. (May 1994). "Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines". Am. J. Respir. Cell Mol. Biol. 10 (5): 471–80. doi:10.1165/ajrcmb.10.5.8179909. PMID 8179909. 
  6. ^ Kaminuma O, Mori A, Kitamura N, Hashimoto T, Kitamura F, Inokuma S et al. (2005). "Role of GATA-3 in IL-5 gene transcription by CD4+ T cells of asthmatic patients". Int. Arch. Allergy Immunol. 137 Suppl 1: 55–9. doi:10.1159/000085433. PMID 15947486. 
  7. ^ Shen H, Ochkur S, McGarry M, Crosby J, Hines E, Borchers M et al. (March 2003). "A causative relationship exists between eosinophils and the development of allergic pulmonary pathologies in the mouse". J. Immunol. 170 (6): 3296–305. doi:10.4049/jimmunol.170.6.3296. PMID 12626589. 
  8. ^ Sanderson C (June 1992). "Interleukin-5, eosinophils, and disease". Blood 79 (12): 3101–9. PMID 1596561. 
  9. ^ Giembycz M, Lindsay M (June 1999). "Pharmacology of the eosinophil". Pharmacol. Rev. 51 (2): 213–340. PMID 10353986. 
  10. ^ Lopez A, Begley C, Williamson D, Warren D, Vadas M, Sanderson C (May 1986). "Murine eosinophil differentiation factor. An eosinophil-specific colony-stimulating factor with activity for human cells". J. Exp. Med. 163 (5): 1085–99. doi:10.1084/jem.163.5.1085. PMC 2188112. PMID 3486243. 
  11. ^ Di Biagio E, Sánchez-Borges M, Desenne J, Suárez-Chacón R, Somoza R, Acquatella G (Jul 1996). "Eosinophilia in Hodgkin's disease: a role for interleukin 5". Int. Arch. Allergy Immunol. 110 (3): 244–51. doi:10.1159/000237294. PMID 8688671. 
  12. ^ Woodcock J, Zacharakis B, Plaetinck G, Bagley C, Qiyu S, Hercus T et al. (November 1994). "Three residues in the common beta chain of the human GM-CSF, IL-3 and IL-5 receptors are essential for GM-CSF and IL-5 but not IL-3 high affinity binding and interact with Glu21 of GM-CSF". EMBO J. 13 (21): 5176–85. PMC 395466. PMID 7957082. 
  13. ^ Johanson K, Appelbaum E, Doyle M, Hensley P, Zhao B, Abdel-Meguid S et al. (April 1995). "Binding interactions of human interleukin 5 with its receptor alpha subunit. Large scale production, structural, and functional studies of Drosophila-expressed recombinant proteins". J. Biol. Chem. 270 (16): 9459–71. doi:10.1074/jbc.270.16.9459. PMID 7721873. 
  14. ^ Murata Y, Takaki S, Migita M, Kikuchi Y, Tominaga A, Takatsu K (February 1992). "Molecular cloning and expression of the human interleukin 5 receptor". J. Exp. Med. 175 (2): 341–51. doi:10.1084/jem.175.2.341. PMC 2119102. PMID 1732409. 
  15. ^ a b Tavernier J, Devos R, Cornelis S, Tuypens T, Van der Heyden J, Fiers W et al. (September 1991). "A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF". Cell 66 (6): 1175–84. doi:10.1016/0092-8674(91)90040-6. PMID 1833065. 
  16. ^ Takaki S, Murata Y, Kitamura T, Miyajima A, Tominaga A, Takatsu K (June 1993). "Reconstitution of the functional receptors for murine and human interleukin 5". J. Exp. Med. 177 (6): 1523–9. doi:10.1084/jem.177.6.1523. PMC 2191058. PMID 8496674. 
  17. ^ Ishino T, Economou N, 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): 7546–56. doi:10.1021/bi2009135. PMID 21770429.