interleukin18

Interleukin-18 (IL-18) is a proinflammatory cytokine of the interleukin-1 (IL-1) family. It is produced by macrophages and other cell types, including dendritic cells, monocytes, keratinocytes, and epithelial cells, as an inactive precursor called pro-IL-18. Processing by the cysteine protease caspase-1 within inflammasomes converts pro-IL-18 into mature IL-18, which is then secreted.

IL-18 exerts its effects by binding to the IL-18 receptor, composed of IL-18Rα and IL-18Rβ subunits, leading to recruitment of the adaptor MyD88 and activation of NF-κB and AP-1 signaling. IL-18 synergizes with IL-12 to robustly induce interferon-gamma (IFN-γ) production from natural killer cells and T cells, promoting Th1-type responses and cytotoxic activity. It can also act on other cell types to drive inflammatory mediators such as IL-1β, TNF-α, and chemokines.

Biological roles include defense against intracellular pathogens and orchestration of inflammatory responses. Dysregulated IL-18 signaling has been linked to a range of inflammatory and autoimmune diseases, and elevated serum IL-18 is observed in conditions such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, adult-onset Still's disease, and inflammatory bowel disease. IL-18 has also been implicated in metabolic and cardiovascular diseases, including obesity-related inflammation and atherosclerosis.

IL-18 activity is tightly controlled by IL-18 binding protein (IL-18BP), a naturally occurring decoy receptor that neutralizes IL-18. Therapeutic approaches using recombinant IL-18BP or other IL-18 inhibitors are under investigation for hyperinflammatory and autoinflammatory disorders, including Still's disease and macrophage activation syndrome, with several agents in clinical development.