Interleukin 5
Type of cytokine
From Wikipedia, the free encyclopedia
Interleukin 5 (IL-5) is an interleukin produced by type-2 T helper cells and mast cells.
Function
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.
Structure
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.[5]
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),[6][7] which are often co-expressed in Th2 cells. IL-5 is also expressed by eosinophils[8] and has been observed in the mast cells of asthmatic airways by immunohistochemistry.[9] IL-5 expression is regulated by several transcription factors including GATA3.[10]
Clinical significance
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.[11] 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.[12]
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[13] and eosinophilic granulomatosis with polyangiitis (EGPA).[14] Another antibody, depemokimab (GSK3511294), ultra-long acting IL-5 inhibitor, is under development.[15]
Some hydroxyethylaminomethylbenzimidazole analogs have shown IL-5 inhibition in vitro.[16]
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.[17] 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,[18] 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.[19]
Interactions
IL-5 has been shown to interact with interleukin 5 receptor alpha subunit.[20][21][22]
Receptors
The IL-5 receptor is composed of an α and a βc chain.[23] 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).[23][24] Glycosylation of the Asn196 residue of the Rα subunit appears to be essential for binding of IL-5.[25]