Theinterleukin-1 receptor antagonist (IL-1RA) is aprotein that in humans is encoded by theIL1RNgene.[5][6]
IL-1RA was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories.[7] IL-1RA is an agent that binds non-productively to the cell surfaceinterleukin-1 receptor (IL-1R), the same receptor that bindsinterleukin 1 family (IL-1), preventing IL-1's from sending a signal to that cell.
IL-1RA is a member of the interleukin 1cytokine family. IL-1RA is secreted by various types of cells including immune cells, epithelial cells, and adipocytes, and is a natural inhibitor of the pro-inflammatory effect of IL1β.[8] This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.[9]
In treatment of temporomandibular joint osteoarthritis (TMJOA) themessenger RNA (mRNA) of IL-1RA can be used. The IL-1RA mRNA reduces pain and joint inflammation by blocking inflammatory cascade signals that lead toosteoarthritis progression.[16]
A recombinant, slightly modified version of interleukin 1 receptor antagonist calledanakinra is used in the treatment ofrheumatoid arthritis, anautoimmune disease in which IL-1 plays a key role.[17] Anakinra differs from native human IL-1RA in that it has the addition of a single methionine residue at its amino terminus[18]
The cytoplasmic and secretedisoforms of IL-1RA can suppress tumors such assquamous cell carcinoma. The cytoplasmic isoform can protect epithelial cells from environmental factors and compete with IL1A in binding with receptors preventing activation. Then, the secreted isoform regulates IL1B in tumor microenvironments by inhibitingglycolysis of IL1B and proliferation of tumor cells, thus preventing the movement of tumor cells.[19]
Interleukin 1 receptor antagonist is used in horses for thetreatment of equine lameness secondary to joint and soft-tissue injury. IL-1RA obstructs the IL1B inflammatory cascade rather than helping to restore damaged tissue.[20]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Steinkasserer A, Spurr NK, Cox S, Jeggo P, Sim RB (July 1992). "The human IL-1 receptor antagonist gene (IL1RN) maps to chromosome 2q14-q21, in the region of the IL-1 alpha and IL-1 beta loci".Genomics.13 (3):654–657.doi:10.1016/0888-7543(92)90137-H.PMID1386337.
^Patterson D, Jones C, Hart I, Bleskan J, Berger R, Geyer D, et al. (January 1993). "The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region".Genomics.15 (1):173–176.doi:10.1006/geno.1993.1025.PMID8432529.
^Kim SJ, Lee HJ, Koo HG, Kim JW, Song JY, Kim MK, et al. (September 2004). "Impact of IL-1 receptor antagonist gene polymorphism on schizophrenia and bipolar disorder".Psychiatric Genetics.14 (3):165–167.doi:10.1097/00041444-200409000-00009.PMID15318032.S2CID43435475.
^Zanardini R, Bocchio-Chiavetto L, Scassellati C, Bonvicini C, Tura GB, Rossi G, et al. (2003). "Association between IL-1beta -511C/T and IL-1RA (86bp)n repeats polymorphisms and schizophrenia".Journal of Psychiatric Research.37 (6):457–462.doi:10.1016/S0022-3956(03)00072-4.PMID14563376.
^Hope S, Melle I, Aukrust P, Steen NE, Birkenaes AB, Lorentzen S, et al. (November 2009). "Similar immune profile in bipolar disorder and schizophrenia: selective increase in soluble tumor necrosis factor receptor I and von Willebrand factor".Bipolar Disorders.11 (7):726–734.doi:10.1111/j.1399-5618.2009.00757.x.hdl:10852/34620.PMID19839997.
Arend WP, Malyak M, Guthridge CJ, Gabay C (1998). "Interleukin-1 receptor antagonist: role in biology".Annual Review of Immunology.16:27–55.doi:10.1146/annurev.immunol.16.1.27.PMID9597123.
Adcock IM, Ito K (June 2000). "Molecular mechanisms of corticosteroid actions".Monaldi Archives for Chest Disease = Archivio Monaldi per le Malattie del Torace.55 (3):256–266.PMID10948677.
Sehouli J, Mustea A, Könsgen D, Katsares I, Lichtenegger W (2003). "Polymorphism of IL-1 receptor antagonist gene: role in cancer".Anticancer Research.22 (6A):3421–3424.PMID12530098.