IL-1β (Interleukin-1 beta)

IL-1β (Interleukin-1 beta) is a pro-inflammatory cytokine produced by monocytes and macrophages, mediating both acute inflammation and inflammaging — the sterile, low-grade systemic inflammation that accumulates with age. Activation requires two signals: a priming signal (e.g., toll-like receptor engagement) drives transcription of inactive pro-IL-1β; a second signal triggers NLRP3 inflammasome assembly, activating caspase-1, which cleaves pro-IL-1β into its secreted form. In aging tissue, senescent cells release IL-1β as part of the SASP, and declining SIRT2-mediated deacetylation of NLRP3 lowers the assembly threshold, sustaining inflammation. Causal involvement in atherosclerosis was shown in CANTOS (Ridker et al., 2017; n = 10,061): canakinumab, a monoclonal antibody neutralising IL-1β, cut major adverse cardiovascular events by 15% (relative) at 150 mg versus placebo, independent of LDL changes. A pre-specified exploratory safety analysis found dose-dependent reductions in lung cancer incidence. Canakinumab is approved for autoinflammatory syndromes but investigational for cardiovascular indications; colchicine, which inhibits NLRP3 assembly via microtubule disruption, received regulatory approval for cardiovascular secondary prevention in several jurisdictions by 2024.