Interleukin-18 receptor complex (IL-18R complex)

The Interleukin-18 receptor complex is a heterodimeric assembly composed of IL-18Rα and IL-18Rβ subunits, both members of the immunoglobulin superfamily. The complex specifically binds the pro-inflammatory cytokine IL-18, triggering conformational receptor changes that recruit the MyD88 adaptor protein and downstream kinases (IRAKs, TRAF6), leading to activation of key immune transcription factors such as NF-κB and the MAP kinase pathway. This signaling results in enhanced production of inflammatory cytokines (including IFN-γ), critical for both host defense and pathological chronic inflammation[1][2][4][7]. Dysregulation of the IL-18/IL-18R pathway has been linked to atherogenesis, autoimmune syndromes, and hyperinflammatory states. The soluble decoy receptor IL-18 binding protein (IL-18BP) tightly regulates IL-18 activity in vivo and serves as a therapeutic antagonist by sequestering IL-18 away from its cell-surface receptors[2][3][5]. The receptor is a validated target for drug development in immunoinflammatory conditions.

Other names

IL-18R complexIL-18Rα/β complexInterleukin-18 receptorIL-18R

Ligand (IL-18) binds to the receptor complex, triggering recruitment of MyD88 adaptor and IRAK kinases, leading to NF-κB and MAPK pathway activation, and increased production of inflammatory cytokines[1][2][4]. Antagonists (e.g., IL-18BP) bind IL-18 and prevent receptor activation, thereby downregulating cytokine production[2][3][5].