Interleukin-18 binding protein (IL-18BP)

Interleukin-18 binding protein is a naturally secreted, glycosylated protein structurally related to immunoglobulin superfamily members, containing three Ig-like domains but lacking a transmembrane region[1]. Encoded on human chromosome 11q13, it consists of 164 amino acids in its mature form and is highly conserved across species[1][6]. IL-18BP is produced constitutively in mononuclear cells and inducible by IFN-γ and certain inflammatory stimuli[4]. It binds IL-18 with ultra-high affinity (dissociation constant ~0.4 nM), surpassing that of the membrane IL-18 receptor, and neutralizes IL-18 at equimolar concentrations[1][2]. This mechanism efficiently suppresses IL-18–mediated immune activation, including Th1 responses and IFN-γ secretion, thus playing a key regulatory role in both physiological and pathological immune responses. Recombinant IL-18BP (e.g., Tadekinig alfa) is in clinical development for the treatment of inflammatory and autoimmune diseases characterized by excessive IL-18 activity[1]. Structural studies reveal both canonical and higher-order assemblies that enhance its inhibitory effectiveness, offering unique opportunities for structure-guided therapeutic innovation[2][3].

Other names

IL18BPInterleukin-18-binding proteinIL-18 antagonist

Direct sequestration and neutralization of IL-18, preventing it from binding and activating IL-18 receptor (IL-18Rα/IL-18Rβ complex); Reduces downstream inflammatory cytokine production, notably IFN-γ, by blocking IL-18-induced signaling