INSRR

IL1RN

The IL1RN gene encodes the interleukin 1 receptor antagonist (IL-1Ra), a critical component of the immune system that modulates the activity of interleukin 1 (IL-1). IL-1 is a cytokine that plays a key role in the inflammatory response, and IL-1Ra serves as a natural inhibitor of this cytokine, preventing excessive inflammation and tissue damage.

Structure

The IL1RN gene is located on chromosome 2q14.2 and consists of four exons. The protein product, IL-1Ra, is a member of the interleukin 1 cytokine family and is structurally similar to IL-1α and IL-1β, but it lacks the ability to bind to the IL-1 receptor and initiate signal transduction. Instead, IL-1Ra competes with IL-1α and IL-1β for binding to the IL-1 receptor, thereby blocking their pro-inflammatory effects.

Function

IL-1Ra is primarily produced by monocytes, macrophages, and other cells in response to inflammatory stimuli. It acts as a competitive inhibitor of IL-1 by binding to the IL-1 receptor without activating it, thus preventing IL-1 from exerting its effects. This regulation is crucial for maintaining the balance of the immune response and preventing chronic inflammation.

Clinical Significance

Mutations or polymorphisms in the IL1RN gene have been associated with various inflammatory and autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. Additionally, recombinant IL-1Ra (anakinra) is used therapeutically to treat conditions like rheumatoid arthritis and other inflammatory disorders by mimicking the natural inhibitory effects of IL-1Ra.

Research and Therapeutic Use

Research into IL1RN and its protein product has led to the development of targeted therapies aimed at modulating the IL-1 pathway. Anakinra, a recombinant form of IL-1Ra, is used to treat rheumatoid arthritis and other inflammatory conditions by reducing inflammation and slowing disease progression.

Genetic Variants

Several polymorphisms in the IL1RN gene have been identified, some of which are associated with altered levels of IL-1Ra production and susceptibility to inflammatory diseases. The most studied polymorphism is a variable number tandem repeat (VNTR) in intron 2, which has been linked to various inflammatory conditions.

Also see

• Interleukin 1
• Cytokine
• Rheumatoid arthritis
• Autoimmune disease
• Inflammation