The interleukin-1 receptor antagonist protein (IL-1RN) is a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
that in humans is encoded by the ''IL1RN''
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
.
IL-1RN was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories.
IL-1RN is an agent that binds non-productively to the cell surface
interleukin-1 receptor
Interleukin-1 receptor (IL-1R) is a cytokine receptor
Cytokine receptors are receptors that bind to cytokines.
In recent years, the cytokine receptors have come to demand the attention of more investigators than cytokines themselves, partly ...
(IL-1R), the same receptor that binds
interleukin 1
The Interleukin-1 family (IL-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.
Discovery
Discovery of these cytokines began with studies on t ...
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
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
family. IL1Ra 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
Interleukin-1 alpha (IL-1 alpha) also known as hematopoietin 1 is a cytokine of the interleukin 1 family that in humans is encoded by the ''IL1A'' gene. In general, Interleukin 1 is responsible for the production of inflammation, as well as the ...
) and interleukin 1, beta (
IL1B
Interleukin-1 beta (IL-1β) also known as leukocytic pyrogen, leukocytic endogenous mediator, mononuclear cell factor, lymphocyte activating factor and other names, is a cytokine protein that in humans is encoded by the ''IL1B'' gene."Catabolin" ...
), 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
Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymph ...
.
Mutations in the IL1RN gene results in a
rare disease
A rare disease is any disease that affects a small percentage of the population. In some parts of the world, an orphan disease is a rare disease whose rarity means there is a lack of a market large enough to gain support and resources for discove ...
called
deficiency of the interleukin-1–receptor antagonist
Deficiency of the interleukin-1–receptor antagonist (DIRA) is an autosomal recessive, genetic autoinflammatory syndrome resulting from mutations in '' IL1RN'', the gene encoding the interleukin 1 receptor antagonist. The mutations result in a ...
(DIRA).
Variants of the IL1RN gene is also associated with risk of schizophrenia.
Elevated levels of IL1RN has been found in serum of schizophrenia patients.
A recombinant, slightly modified version of interleukin 1 receptor antagonist called
anakinra
Anakinra, sold under the brand name Kineret, is a biopharmaceutical medication used to treat rheumatoid arthritis, cryopyrin-associated periodic syndromes, familial Mediterranean fever, and Still's disease. It is a recombinant and slightly modif ...
is used in the treatment of
rheumatoid arthritis
Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involv ...
, an
autoimmune
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...
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
Use in horses
Interleukin 1 receptor antagonist is used in horses for the
treatment of equine lameness The treatment of equine lameness is a complex subject. Lameness in horses has a variety of causes, and treatment must be tailored to the type and degree of injury, as well as the financial capabilities of the owner. Treatment may be applied locally ...
secondary to joint and soft-tissue injury.
References
Further reading
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External links
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{{Interleukin receptor modulators
Cytokines