IL-18

Class

half-life-extended IL-18 binding protein (IL-18BP) fusion

Pathway

neutralizes IL-18 cytokine signaling implicated in atopic dermatitis inflammation

Interleukin-18 (IL-18) is a signaling protein belonging to the IL-1 cytokine family that helps orchestrate innate and adaptive immune responses. It is produced as an inactive precursor inside cells and is activated by intracellular protein complexes called inflammasomes before being released to act on nearby immune cells bearing its receptor. Once engaged, IL-18 signaling promotes production of interferon-gamma and other inflammatory mediators, amplifying immune activation. In chronic inflammatory skin conditions such as atopic dermatitis, sustained IL-18 activity is thought to contribute to the itch-inflammation cycle that damages the skin barrier and perpetuates disease. The body naturally restrains IL-18 through a circulating decoy protein, IL-18 binding protein (IL-18BP), which binds IL-18 with high affinity and prevents it from reaching its receptor. Therapeutic approaches built on this biology aim to neutralize excess IL-18 signaling, either by engineering a longer-lasting version of the natural binding protein (a half-life-extended IL-18BP fusion) or by using an antibody that directly targets the cytokine. Both strategies pursue the same end point—reducing available active IL-18—but differ in how closely they mimic natural regulatory biology versus using a wholly engineered binding surface. This mechanism is of broader interest across inflammatory and autoinflammatory diseases where IL-18 overactivity has been implicated.