Interleukin-1 Beta

The cytokine interleukin-1β (IL-1β) is a key mediator of the inflammatory response, essential for host defense and resistance to pathogens. ^[1] While essential for the host response, IL-1β also exacerbates damage during chronic disease and acute tissue injury. ^[1] IL-1β is one of the pro-inflammatory cytokines, alongside IL-6 and tumor necrosis factor-α, that are secreted by macrophages and other cells during inflammation. ^{[2] [3]}

IL-1β is produced as an inactive 31 kDa precursor, termed pro-IL-1β, in response to pathogen-associated molecular patterns acting through pattern recognition receptors on macrophages, in a step generally referred to as priming. ^[1] Pro-IL-1β is cleaved by the pro-inflammatory protease caspase-1, whose activation occurs via recruitment to a multi-protein complex termed the inflammasome, the best characterized of which is formed by the cytosolic pattern recognition receptor NLRP3. ^[1] Following tissue injury, activation of the NLRP3 inflammasome results in cytokine production, primarily IL-1β and IL-18, and eventually the inflammatory cell death known as pyroptosis. ^[4] IL-1β secretion does not follow the conventional ER-Golgi route of secretion, and its mechanism of release has proven elusive. ^[1]