Il-1 Receptor Antagonist, Soluble (IL-1 receptor) Human Active Protein

The protein encoded by this gene is a member of the interleukin 1 cytokine family. 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. A polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures and gastric cancer. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

Function: Inhibits the activity of interleukin-1 by binding to receptor IL1R1 and preventing its association with the coreceptor IL1RAP for signaling. Has no interleukin-1 like activity. Binds functional interleukin-1 receptor IL1R1 with greater affinity than decoy receptor IL1R2; however, the physiological relevance of the latter association is unsure. Ref.17

Subcellular location: Isoform 1: Secreted. Isoform 2: Cytoplasm. Isoform 3: Cytoplasm. Isoform 4: Cytoplasm.

Tissue specificity: The intracellular form of IL1RN is predominantly expressed in epithelial cells.

Involvement in disease: Microvascular complications of diabetes 4 (MVCD4) [MIM:612628]: Pathological conditions that develop in numerous tissues and organs as a consequence of diabetes mellitus. They include diabetic retinopathy, diabetic nephropathy leading to end-stage renal disease, and diabetic neuropathy. Diabetic retinopathy remains the major cause of new-onset blindness among diabetic adults. It is characterized by vascular permeability and increased tissue ischemia and angiogenesis.Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.Interleukin 1 receptor antagonist deficiency (DIRA) [MIM:612852]: A rare autoinflammatory disease of skin and bone resulting in sterile multifocal osteomyelitis, periostitis, and pustulosis from birth. The term autoinflammatory disease describes a group of disorders characterized by attacks of seemingly unprovoked inflammation without significant levels of autoantibodies and autoreactive T-cells.Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.21

Pharmaceutical use: Available under the name Kineret (Amgen). Used for the reduction in signs and symptoms and slowing the progression of structural damage in moderately to severely active rheumatoid arthritis.