IL1

Interleukin-1 (IL-1) refers to a family of cytokines that play a central role in the regulation of inflammatory and immune responses. The two best characterized members are IL-1 alpha (IL-1α) and IL-1 beta (IL-1β), which share similar biological activities but differ in expression, processing, and release. A related protein, the IL-1 receptor antagonist (IL-1Ra, encoded by IL1RN), inhibits IL-1 signaling by occupying the IL-1 receptor without triggering intracellular responses.

IL-1 production and signaling involve distinct pathways. IL-1α is constitutively produced by many cell types and can act as an alarmin when cells are damaged; IL-1β is produced as an inactive proprotein in response to inflammatory stimuli and requires processing by caspase-1 within the inflammasome to become active. Signaling occurs when IL-1 binds to the IL-1 receptor type I (IL-1RI) in conjunction with the IL-1 receptor accessory protein (IL-1RAcP); this triggers downstream inflammatory gene expression. IL-1 receptor type II (IL-1RII) can act as a decoy receptor, limiting IL-1 activity. IL-1 production and action are tightly regulated, with dysregulation contributing to autoinflammatory and chronic inflammatory diseases.

Functions of IL-1 include induction of fever, hepatic production of acute-phase proteins such as C-reactive protein, upregulation of adhesion molecules, chemokine production, and promotion of leukocyte recruitment. It also influences bone resorption and has widespread effects on metabolism and neuroendocrine responses. In clinical medicine, IL-1 signaling is a therapeutic target in several autoinflammatory conditions and chronic inflammatory diseases.

Therapeutic blockade of IL-1 is achieved with agents such as anakinra (IL-1 receptor antagonist), canakinumab (anti-IL-1β antibody), and rilonacept (a soluble IL-1 receptor fusion protein). These therapies are used for conditions including CAPS, systemic juvenile idiopathic arthritis, gout, and recurrent pericarditis, among others.