Interleukin-1 receptor antagonist explained

The interleukin-1 receptor antagonist (IL-1RA) is a protein that in humans is encoded by the IL1RN gene.[1] [2]

IL-1RA was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories.[3] IL-1RA is an agent that binds non-productively to the cell surface interleukin-1 receptor (IL-1R), the same receptor that binds interleukin 1 family (IL-1), preventing IL-1's from sending a signal to that cell.

Function

IL-1RA is a member of the interleukin 1 cytokine 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.[4] 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.[5]

Clinical significance

A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures[6] and gastric cancer.[7]

Biallelic deleterious mutations in the IL1RN gene results in a rare autoinflammatory disease called deficiency of the interleukin-1–receptor antagonist (DIRA).[8] Variants of the IL1RN gene is also associated with risk of schizophrenia.[9] [10] Elevated levels of IL-1RA has been found in serum of schizophrenia patients.[11]

In treatment of temporomandibular joint osteoarthritis (TMJOA) the messenger RNA (mRNA) of IL-1RA can be used. The IL-1RA mRNA reduces pain and joint inflammation by blocking inflammatory cascade signals that lead to osteoarthritis progression.[12]

A recombinant, slightly modified version of interleukin 1 receptor antagonist called anakinra is used in the treatment of rheumatoid arthritis, an autoimmune disease in which IL-1 plays a key role.[13] Anakinra differs from native human IL-1RA in that it has the addition of a single methionine residue at its amino terminus [14]

The cytoplasmic and secreted isoforms of IL-1RA can suppress tumors such as squamous 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 inhibiting glycolysis of IL1B and proliferation of tumor cells, thus preventing the movement of tumor cells.[15]

Use in horses

Interleukin 1 receptor antagonist is used in horses for the treatment of equine lameness secondary to joint and soft-tissue injury. IL-1RA obstructs the IL1B inflammatory cascade rather than helping to restore damaged tissue.[16]

Further reading

Notes and References

  1. Steinkasserer A, Spurr NK, Cox S, Jeggo P, Sim RB . 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 . July 1992 . 1386337 . 10.1016/0888-7543(92)90137-H .
  2. Patterson D, Jones C, Hart I, Bleskan J, Berger R, Geyer D, Eisenberg SP, Smith MF, Arend WP . The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region . Genomics . 15 . 1 . 173–176 . January 1993 . 8432529 . 10.1006/geno.1993.1025 .
  3. Dinarello CA . The interleukin-1 family: 10 years of discovery . FASEB Journal . 8 . 15 . 1314–1325 . December 1994 . 8001745 . 10.1096/fasebj.8.15.8001745 . 10404996 . free .
  4. Perrier S, Darakhshan F, Hajduch E . IL-1 receptor antagonist in metabolic diseases: Dr Jekyll or Mr Hyde? . FEBS Letters . 580 . 27 . 6289–6294 . November 2006 . 17097645 . 10.1016/j.febslet.2006.10.061 . 23087836 . free . 2006FEBSL.580.6289P .
  5. Web site: Entrez Gene: IL1RN interleukin 1 receptor antagonist.
  6. Langdahl BL, Løkke E, Carstens M, Stenkjaer LL, Eriksen EF . Osteoporotic fractures are associated with an 86-base pair repeat polymorphism in the interleukin-1--receptor antagonist gene but not with polymorphisms in the interleukin-1beta gene . Journal of Bone and Mineral Research . 15 . 3 . 402–414 . March 2000 . 10750554 . 10.1359/jbmr.2000.15.3.402 . 23035139 . free .
  7. El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, Herrera J, Lissowska J, Yuan CC, Rothman N, Lanyon G, Martin M, Fraumeni JF, Rabkin CS . Interleukin-1 polymorphisms associated with increased risk of gastric cancer . Nature . 404 . 6776 . 398–402 . March 2000 . 10746728 . 10.1038/35006081 . 1288472 . 2000Natur.404..398E .
  8. Aksentijevich I, Masters SL, Ferguson PJ, Dancey P, Frenkel J, van Royen-Kerkhoff A, Laxer R, Tedgård U, Cowen EW, Pham TH, Booty M, Estes JD, Sandler NG, Plass N, Stone DL, Turner ML, Hill S, Butman JA, Schneider R, Babyn P, El-Shanti HI, Pope E, Barron K, Bing X, Laurence A, Lee CC, Chapelle D, Clarke GI, Ohson K, Nicholson M, Gadina M, Yang B, Korman BD, Gregersen PK, van Hagen PM, Hak AE, Huizing M, Rahman P, Douek DC, Remmers EF, Kastner DL, Goldbach-Mansky R . An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist . The New England Journal of Medicine . 360 . 23 . 2426–2437 . June 2009 . 19494218 . 2876877 . 10.1056/NEJMoa0807865 .
  9. Kim SJ, Lee HJ, Koo HG, Kim JW, Song JY, Kim MK, Shin DH, Jin SY, Hong MS, Park HJ, Yoon SH, Park HK, Chung JH . Impact of IL-1 receptor antagonist gene polymorphism on schizophrenia and bipolar disorder . Psychiatric Genetics . 14 . 3 . 165–167 . September 2004 . 15318032 . 10.1097/00041444-200409000-00009 . 43435475 .
  10. Zanardini R, Bocchio-Chiavetto L, Scassellati C, Bonvicini C, Tura GB, Rossi G, Perez J, Gennarelli M . Association between IL-1beta -511C/T and IL-1RA (86bp)n repeats polymorphisms and schizophrenia . Journal of Psychiatric Research . 37 . 6 . 457–462 . 2003 . 14563376 . 10.1016/S0022-3956(03)00072-4 .
  11. Hope S, Melle I, Aukrust P, Steen NE, Birkenaes AB, Lorentzen S, Agartz I, Ueland T, Andreassen OA . 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 . November 2009 . 19839997 . 10.1111/j.1399-5618.2009.00757.x . free . 10852/34620 .
  12. Deng J, Fukushima Y, Nozaki K, Nakanishi H, Yada E, Terai Y, Fueki K, Itaka K . Anti-Inflammatory Therapy for Temporomandibular Joint Osteoarthritis Using mRNA Medicine Encoding Interleukin-1 Receptor Antagonist . Pharmaceutics . 14 . 9 . 1785 . August 2022 . 36145533 . 9505648 . 10.3390/pharmaceutics14091785 . free .
  13. Mertens M, Singh JA . Anakinra for rheumatoid arthritis . The Cochrane Database of Systematic Reviews . 1 . CD005121 . January 2009 . 19160248 . 10.1002/14651858.CD005121.pub3 .
  14. Web site: Kineret (anakinra) injection, for subcutaneous use . Swedish Orphan Biovitrum .
  15. Ding . Yujie . Yi . Jie . Wang . Jinxin . Sun . Zhida . April 2023 . Interleukin-1 receptor antagonist: a promising cytokine against human squamous cell carcinomas . Heliyon . en . 9 . 4 . e14960 . 10.1016/j.heliyon.2023.e14960 . free . 10070157 . 37025835. 2023Heliy...914960D .
  16. Smith . Emily J. . Beaumont . Ross E. . McClellan . Alyce . Sze . Cheryl . Palomino Lago . Esther . Hazelgrove . Liberty . Dudhia . Jayesh . Smith . Roger K. W. . Guest . Deborah J. . March 2023 . Tumour necrosis factor alpha, interleukin 1 beta and interferon gamma have detrimental effects on equine tenocytes that cannot be rescued by IL-1RA or mesenchymal stromal cell–derived factors . Cell and Tissue Research . en . 391 . 3 . 523–544 . 10.1007/s00441-022-03726-6 . 0302-766X . 9974687 . 36543895.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Interleukin-1 receptor antagonist".

Except where otherwise indicated, Everything.Explained.Today is © Copyright 2009-2024, A B Cryer, All Rights Reserved. Cookie policy.