Similarly to IL-1β, the IL-18 precursor is processed intracellularly by caspase 1 in the NLRP3 inflammasome into its mature biologically active molecule of 18 kDa.
[12] IL-18 receptor consists of the inducible component IL-18Rα, which binds the mature IL-18 with low affinity and the constitutively expressed co-receptor IL-18Rβ.
This signaling domain recruits the MyD88 adaptor protein that activates proinflammatory programs and NF-κB pathway.
[15] Moreover, IL-37 binds to single immunoglobulin IL-1 receptor related protein (SIGIRR), also known as IL-1R8 or TIR8, which forms a complex with IL-18Rα and induces an anti-inflammatory response.
[19] High levels of IL18 have also been described in essential hypertensive subjects[20] Endometrial IL-18 receptor mRNA and the ratio of IL-18 binding protein to interleukin 18 is significantly increased in adenomyosis patients in comparison to normal people, indicating a role in its pathogenesis.
[22] IL-18 has also been found to increase the Alzheimer's disease-associated amyloid-beta production in human neuron cells.
[23] IL-18 is also associated with urine protein excretion which means that it can be marker for assessing the progression of diabetic nephropathy.