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Interleukins (ILs) are a group of cytokines that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related proteins.
Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene.
Interleukin 12 (IL-12) is an interleukin that is naturally produced by dendritic cells, macrophages, neutrophils, helper T cells and human B-lymphoblastoid cells (NC-37) in response to antigenic stimulation. IL-12 belongs to the family of interleukin-12. IL-12 family is unique in comprising the only heterodimeric cytokines, which includes IL-12, IL-23, IL-27 and IL-35. Despite sharing many structural features and molecular partners, they mediate surprisingly diverse functional effects.
The interleukin 4 is a cytokine that induces differentiation of naive helper T cells (Th0 cells) to Th2 cells. Upon activation by IL-4, Th2 cells subsequently produce additional IL-4 in a positive feedback loop. IL-4 is produced primarily by mast cells, Th2 cells, eosinophils and basophils. It is closely related and has functions similar to IL-13.
Caspase-1/Interleukin-1 converting enzyme (ICE) is an evolutionarily conserved enzyme that proteolytically cleaves other proteins, such as the precursors of the inflammatory cytokines interleukin 1β and interleukin 18 as well as the pyroptosis inducer Gasdermin D, into active mature peptides. It plays a central role in cell immunity as an inflammatory response initiator. Once activated through formation of an inflammasome complex, it initiates a proinflammatory response through the cleavage and thus activation of the two inflammatory cytokines, interleukin 1β (IL-1β) and interleukin 18 (IL-18) as well as pyroptosis, a programmed lytic cell death pathway, through cleavage of Gasdermin D. The two inflammatory cytokines activated by Caspase-1 are excreted from the cell to further induce the inflammatory response in neighboring cells.
Interleukin 30 (IL-30) forms one chain of the heterodimeric cytokine called interleukin 27 (IL-27), thus it is also called IL27-p28. IL-27 is composed of α chain p28 and β chain Epstain-Barr induce gene-3 (EBI3). The p28 subunit, or IL-30, has an important role as a part of IL-27, but it can be secreted as a separate monomer and has its own functions in the absence of EBI3. The discovery of IL-30 as individual cytokine is relatively new and thus its role in the modulation of the immune response is not fully understood.
Interleukin-25 (IL-25) – also known as interleukin-17E (IL-17E) – is a protein that in humans is encoded by the IL25 gene on chromosome 14. IL-25 was discovered in 2001 and is made up of 177 amino acids.
Interleukin-22 (IL-22) is protein that in humans is encoded by the IL22 gene.
Interleukin 17 family is a family of pro-inflammatory cystine knot cytokines. They are produced by a group of T helper cell known as T helper 17 cell in response to their stimulation with IL-23. Originally, Th17 was identified in 1993 by Rouvier et al. who isolated IL17A transcript from a rodent T-cell hybridoma. The protein encoded by IL17A is a founding member of IL-17 family. IL17A protein exhibits a high homology with a viral IL-17-like protein encoded in the genome of T-lymphotropic rhadinovirus Herpesvirus saimiri. In rodents, IL-17A is often referred to as CTLA8.
Interleukin 19 (IL-19) is an immunosuppressive protein that belongs to the IL-10 cytokine subfamily.
Interleukin 35 (IL-35) is a recently discovered anti-inflammatory cytokine from the IL-12 family. Member of IL-12 family - IL-35 is produced by wide range of regulatory lymphocytes and plays a role in immune suppression. IL-35 can block the development of Th1 and Th17 cells by limiting early T cell proliferation.
Interleukin 37 (IL-37), also known as Interleukin-1 family member 7 (IL-1F7), is an anti-inflammatory cytokine important for the downregulation of pro-inflammatory cytokine production as well as the suppression of tumor cell growth.
Interleukin 20 receptor, alpha subunit, is a subunit of the interleukin-20 receptor, the interleukin-26 receptor, and the interleukin-24 receptor. The interleukin 20 receptor, alpha subunit is also referred to as IL20R1 or IL20RA. The IL20RA receptor is involved in both pro-inflammatory and anti-inflammatory responses, signaling through the JAK-STAT pathway.
Interleukin 20 receptor, beta subunit is a subunit of the interleukin-20 receptor and interleukin-22 receptor. It is believed to be involved in both pro-inflammatory and anti-inflammatory responses.
Interleukin 20 receptors (IL20R) belong to the IL-10 family. IL20R are involved in both pro-inflammatory and anti-inflammatory immune response. There are two types of IL20R: Type I and Type II.
Interleukin-17A is a protein that in humans is encoded by the IL17A gene. In rodents, IL-17A used to be referred to as CTLA8, after the similarity with a viral gene.
The Interleukin-1 family is a group of 11 cytokines that plays a central role in the regulation of immune and inflammatory responses to infections or sterile insults.
Interleukin 23 (IL-23) is a heterodimeric cytokine composed of an IL-12B (IL-12p40) subunit and an IL-23A (IL-23p19) subunit. IL-23 is part of the IL-12 family of cytokines. The functional receptor for IL-23 consists of a heterodimer between IL-12Rβ1 and IL-23R.
Olamkicept, also known as soluble gp130Fc or sgp130Fc is an immunosuppressive drug candidate, which selectively blocks activities of the cytokine Interleukin-6, which are mediated by the soluble Interleukin-6. Interleukin-6 is a cytokine, which plays a dominant role in the regulation of the immune response and also in autoimmunity. Furthermore, Interleukin-6 has been demonstrated to be involved in the regulation of metabolism and body weight. Interleukin-6 also has many activities on neural cells. The biochemical principle was invented by the German biochemist Stefan Rose-John and it was further developed into a biotech compound by the Conaris Research Institute AG, which gave an exclusive world-wide license to the Swiss-based biopharmaceutical company Ferring Pharmaceuticals. In December 2016, Ferring and the biotech company I-MAB signed a licensing agreement granting I-MAB exclusive rights in Asia to Olamkicept for the treatment of autoimmune disease.
Hyper-IL-6 is a designer cytokine, which was generated by the German biochemist Stefan Rose-John. Hyper-IL-6 is a fusion protein of the four-helical cytokine Interleukin-6 and the soluble Interleukin-6 receptor which are covalently linked by a flexible peptide linker. Interleukin-6 on target cells binds to a membrane bound Interleukin-6 receptor. The complex of Interleukin-6 and the Interleukin-6 receptor associate with a second receptor protein called gp130, which dimerises and initiates intracellular signal transduction. Gp130 is expressed on all cells of the human body whereas the Interleukin-6 receptor is only found on few cells such as hepatocytes and some leukocytes. Neither Interleukin-6 nor the Interleukin-6 receptor have a measurable affinity for gp130. Therefore, cells, which only express gp130 but no Interleukin-6 receptor are not responsive to Interleukin-6. It was found, however, that the membrane-bound Interleukin-6 receptor can be cleaved from the cell membrane generating a soluble Interleukin-6 receptor. The soluble Interleukin-6 receptor can bind the ligand Interleukin-6 with similar affinity as the membrane-bound Interleukin-6 receptor and the complex of Interleukin-6 and the soluble Interleukin-6 receptor can bind to gp130 on cells, which only express gp130 but no Interleukin-6 receptor. The mode of signaling via the soluble Interleukin-6 receptor has been named Interleukin-6 trans-signaling whereas Interleukin-6 signaling via the membrane-bound Interleukin-6 receptor is referred to as Interleukin-6 classic signaling. Therefore, the generation of the soluble Interleukin-6 receptor enables cells to respond to Interleukin-6, which in the absence of soluble Interleukin-6 receptor would be completely unresponsive to the cytokine.
References
- 1 2 3 4 "About the Editors | Nature Reviews Endocrinology". www.nature.com. Retrieved 3 April 2022.
- ↑ Hunter, Christopher A., and Simon A. Jones. "IL-6 as a keystone cytokine in health and disease." Nature immunology 16.5 (2015): 448-457.
- ↑ Scheller, Jürgen, et al. "The pro-and anti-inflammatory properties of the cytokine interleukin-6." Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1813.5 (2011): 878-888.
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