Figure 1.

IL‐18 regulation by IL‐18 binding protein and IL‐37. IL‐18 binds the ligand receptor IL‐18Rα, inducing the recruitment of IL‐18Rβ to form a high affinity receptor. The Toll‐IL‐1R Receptor (TIR) domains approximate and allow the binding of MyD88, then inducing a pro‐inflammatory signal into the cells terminating in NF‐κB activation. IL‐18 binding protein (IL‐18BP) which is present in the extracellular compartment may bind soluble mature IL‐18 with a higher affinity than IL‐18Rα and prevents IL‐18 binding to IL‐18 receptor. IL‐18BP may also bind IL‐37, preventing its binding to IL‐18Rα. Free IL‐37 binds to IL‐18Rα inducing the recruitment of IL‐1R8 to form a high affinity receptor, which does not bind MyD88, but induces instead an anti‐inflammatory signal into the cell