Interleukin-1 receptor antagonist

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. 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.

Clinical significance

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

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

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.

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. Anakinra differs from native human IL-1RA in that it has the addition of a single methionine residue at its amino terminus

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.

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.

References

References

1. (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.
2. (January 1993). "The human interleukin-1 receptor antagonist (IL1RN) gene is located in the chromosome 2q14 region". Genomics.
3. (December 1994). "The interleukin-1 family: 10 years of discovery". FASEB Journal.
4. (November 2006). "IL-1 receptor antagonist in metabolic diseases: Dr Jekyll or Mr Hyde?". FEBS Letters.
5. "IL1RN interleukin 1 receptor antagonist". National Center for Biotechnology Information (NCBI), U.S. National Library Medicine.
6. (March 2000). "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.
7. (March 2000). "Interleukin-1 polymorphisms associated with increased risk of gastric cancer". Nature.
8. (June 2009). "An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist". The New England Journal of Medicine.
9. (September 2004). "Impact of IL-1 receptor antagonist gene polymorphism on schizophrenia and bipolar disorder". Psychiatric Genetics.
10. (2003). "Association between IL-1beta -511C/T and IL-1RA (86bp)n repeats polymorphisms and schizophrenia". Journal of Psychiatric Research.
11. (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.
12. (August 2022). "Anti-Inflammatory Therapy for Temporomandibular Joint Osteoarthritis Using mRNA Medicine Encoding Interleukin-1 Receptor Antagonist". Pharmaceutics.
13. (January 2009). "Anakinra for rheumatoid arthritis". The Cochrane Database of Systematic Reviews.
14. "Kineret (anakinra) injection, for subcutaneous use". Swedish Orphan Biovitrum.
15. (April 2023). "Interleukin-1 receptor antagonist: a promising cytokine against human squamous cell carcinomas". Heliyon.
16. (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.