interleukin1

Interleukin-1 (IL-1) refers to a group of cytokines in the interleukin-1 family that play a central role in mediating the body's inflammatory and immune responses. The two best characterized members are interleukin-1 alpha (IL-1α) and interleukin-1 beta (IL-1β). A related molecule, interleukin-1 receptor antagonist (IL-1ra), inhibits IL-1 signaling by blocking receptor access.

IL-1α is produced constitutively by many cell types and can be released actively by necrotic cells; IL-1β is synthesized as an inactive pro-IL-1β that requires proteolytic cleavage by caspase-1 within the inflammasome to become active. Production is typically triggered by pathogens, tissue injury, or other inflammatory stimuli. IL-1 signals through the IL-1 receptor type I (IL-1R1) in conjunction with the IL-1 receptor accessory protein (IL-1RAcP); IL-1 receptor type II can act as a decoy receptor. Signaling is primarily MyD88-dependent and activates NF-κB and MAPK pathways, leading to transcription of inflammatory genes.

The systemic effects include fever, increased expression of acute-phase proteins such as C-reactive protein, and recruitment of leukocytes to sites of injury or infection.

IL-1 signaling is tightly regulated by natural antagonists and inhibitors; IL-1ra competes for IL-1R1, and in some contexts IL-1 receptor type II reduces signaling. The IL-1 family also includes other members with distinct roles.

Clinically, IL-1 contributes to autoinflammatory and autoimmune diseases, including cryopyrin-associated periodic syndromes (CAPS), rheumatoid arthritis, and gout. Therapies that block IL-1 signaling, such as anakinra (recombinant IL-1ra), canakinumab (anti-IL-1β antibody), and rilonacept (IL-1 trap), are used to treat these conditions and reduce inflammatory flares.

Genes encoding IL-1α and IL-1β (IL1A and IL1B) and the IL-1 receptor antagonist (IL1RN) are part of the IL-1 gene cluster in humans.