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]
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.[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]
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.[13] 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,[14] 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.
The IL-5 receptor is composed of an α and a βc chain.[19] 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).[19][20] Glycosylation of the Asn196 residue of the Rα subunit appears to be essential for binding of IL-5.[21]
References
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^Bradding P, Roberts JA, Britten KM, 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". American Journal of Respiratory Cell and Molecular Biology. 10 (5): 471–480.
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^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". International Archives of Allergy and Immunology. 137 (Suppl 1): 55–59.
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^Berti A, Atzeni F, Dagna L, Del Giacco S, Emmi G, Salvarani C, Vaglio A (February 2023). "Targeting the interleukin-5 pathway in EGPA: evidence, uncertainties and opportunities". Annals of the Rheumatic Diseases. 82 (2): 164–168.
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^Boggu PR, Kim Y, Jung SH (November 2019). "Discovery of benzimidazole analogs as a novel interleukin-5 inhibitors". European Journal of Medicinal Chemistry. 181: 111574.
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^Giembycz MA, Lindsay MA (June 1999). "Pharmacology of the eosinophil". Pharmacological Reviews. 51 (2): 213–340.
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^Di Biagio E, Sánchez-Borges M, Desenne JJ, Suárez-Chacón R, Somoza R, Acquatella G (July 1996). "Eosinophilia in Hodgkin's disease: a role for interleukin 5". International Archives of Allergy and Immunology. 110 (3): 244–251.
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^
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". Cell. 66 (6): 1175–1184.
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