Interleukin 18 (IL-18) (IL-18)

Interleukin 18 (IL-18) is a potent pro-inflammatory cytokine of the IL-1 family, originally identified as an interferon-gamma-inducing factor (IGIF) (UniProt Q14116). It is synthesized as an inactive precursor (pro-IL-18) that requires proteolytic cleavage, primarily by caspase-1 within an inflammasome complex, to become biologically active and be released from the cell (PMID: 23545280). Once active, IL-18 binds to its heterodimeric receptor (IL-18Rα and IL-18Rβ) to stimulate the production of interferon-gamma (IFN-γ) and enhance the cytolytic activity of T cells and natural killer (NK) cells (PMID: 11169395). Dysregulation of IL-18 production and release is a hallmark of several autoinflammatory and autoimmune conditions, including Adult-onset Still's disease (AOSD) and Macrophage Activation Syndrome (MAS) (PMID: 18080035). Therapeutic strategies focus on neutralizing IL-18 using recombinant human IL-18 binding protein (Tadekinig alfa) or monoclonal antibodies to mitigate systemic inflammation (DrugBank DB12853). Conversely, IL-18 agonists are being explored in oncology to leverage its ability to stimulate anti-tumor immune responses.

Other names

Interferon-gamma-inducing factorIGIFIL-1 gammaInterleukin-1 family member 4IL1F4

Neutralization of the cytokine by binding proteins (e.g., IL-18BP) or monoclonal antibodies to prevent its interaction with the IL-18 receptor complex (IL-18Rα and IL-18Rβ), thereby inhibiting downstream pro-inflammatory signaling and IFN-γ production.