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.
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. 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.
Eosinophils are terminally differentiatedgranulocytes 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. 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, 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.
The IL-5 receptor is composed of an α and a βc chain. 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). Glycosylation of the Asn196 residue of the Rα subunit appears to be essential for binding of IL-5.
^Milburn MV, Hassell AM, Lambert MH, Jordan SR, Proudfoot AE, Graber P, Wells TN (May 1993). "A novel dimer configuration revealed by the crystal structure at 2.4 A resolution of human interleukin-5". Nature363 (6425): 172–6. doi:10.1038/363172a0. PMID8483502.
^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". Somat. Cell Mol. Genet.15 (2): 143–52. doi:10.1007/BF01535075. PMID2784591.
^van Leeuwen BH, Martinson ME, Webb GC, Young IG (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". Blood73 (5): 1142–8. PMID2564789.
^Bradding P, Roberts JA, Britten KM, Montefort S, Djukanovic R, Mueller R, Heusser CH, Howarth PH, Holgate ST (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. PMID8179909.
^Kaminuma O, Mori A, Kitamura N, Hashimoto T, Kitamura F, Inokuma S, Miyatake S (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. PMID15947486.
^Shen HH, Ochkur SI, McGarry MP, Crosby JR, Hines EM, Borchers MT, Wang H, Biechelle TL, O'Neill KR, Ansay TL, Colbert DC, Cormier SA, Justice JP, Lee NA, Lee JJ (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. PMID12626589.
^Sanderson CJ (June 1992). "Interleukin-5, eosinophils, and disease". Blood79 (12): 3101–9. PMID1596561.
^Giembycz MA, Lindsay MA (June 1999). "Pharmacology of the eosinophil". Pharmacol. Rev.51 (2): 213–340. PMID10353986.
^Johanson K, Appelbaum E, Doyle M, Hensley P, Zhao B, Abdel-Meguid SS, Young P, Cook R, Carr S, Matico R (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. PMID7721873.
^ abTavernier J, Devos R, Cornelis S, Tuypens T, Van der Heyden J, Fiers W, Plaetinck G (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". Cell66 (6): 1175–84. doi:10.1016/0092-8674(91)90040-6. PMID1833065.