IL1RN

Interleukin-1 receptor antagonist (IL-1Ra) is a member of the interleukin-1 family and is produced by the IL1RN gene in humans. The protein acts as a natural inhibitor of interleukin-1 signaling by binding to the IL-1 receptor type I (IL-1R1) in complex with the IL-1 receptor accessory protein (IL-1RAcP) without triggering signal transduction. This competitive antagonism blocks the activities of IL-1α and IL-1β, helping to limit inflammatory responses. The mature secreted form of IL-1Ra is approximately 17 kDa and is encoded by multiple splice variants, including secreted and intracellular forms.

The IL1RN gene is located on chromosome 2 in humans and is expressed in a range of tissues, with notable production by monocytes and other immune cells. Its expression is upregulated in response to inflammatory stimuli, contributing to a negative feedback mechanism that helps temper IL-1–driven inflammation.

Clinical significance of IL1RN lies primarily in disorders of dysregulated IL-1 signaling. Rare biallelic mutations in IL1RN cause deficiency of the IL-1 receptor antagonist (DIRA), an autoinflammatory disease characterized by neonatal-onset multifocal osteomyelitis, bone lesions, fever, and pustular skin lesions; treatment with IL-1 blockade, notably anakinra, canakinumab, or related therapies, is effective. More common genetic variants in IL1RN have been studied for associations with inflammatory and metabolic diseases, reflecting the role of IL-1Ra in controlling inflammatory cascades. In medicine, recombinant IL-1Ra (anakinra) is used to treat rheumatoid arthritis and a range of autoinflammatory syndromes, illustrating the therapeutic potential of IL-1 pathway modulation.