IL1beta

IL-1β is a potent pro-inflammatory cytokine of the interleukin-1 family, primarily produced by activated macrophages, monocytes, dendritic cells, and some epithelial cells. It is encoded by the IL1B gene in humans and plays a central role in innate immune responses and inflammation.

IL-1β is synthesized as an inactive precursor, pro-IL-1β, which lacks secretion signals. Cleavage by active caspase-1 within the inflammasome (for example NLRP3) generates the mature, biologically active IL-1β. Release is typically linked to cell damage or pyroptotic lysis and stimuli such as PAMPs and DAMPs.

IL-1β exerts its effects by binding to the IL-1 receptor type I (IL-1R1) with the IL-1 receptor accessory protein (IL-1RAcP). Receptor engagement recruits the adaptor MyD88 and activates signaling cascades including IRAK, TRAF6, NF-κB, and MAP kinases, leading to transcription of inflammatory genes.

The cytokine drives fever through the hypothalamus and promotes expression of prostaglandins, chemokines, adhesion molecules, and acute-phase proteins by the liver. It mediates leukocyte recruitment and amplifies inflammatory responses, contributing to tissue damage in chronic or excessive inflammation.

Dysregulated IL-1β signaling is linked to autoinflammatory and autoimmune diseases, such as cryopyrin-associated periodic syndromes, rheumatoid arthritis, and gout. Therapeutic agents include canakinumab (anti-IL-1β monoclonal antibody), rilonacept (IL-1 trap), and anakinra (IL-1 receptor antagonist), which reduce IL-1β–mediated pathology.