Interleukin-36 (IL-36) is part of the larger IL-1 family of cytokines and includes three agonists, IL-36α, IL-36β and IL-36γ, and two inhibitors, IL-36RA and IL-38. IL-36α is proteolytically cleaved to its active form, primarily by neutrophil proteases, yielding an active cytokine. IL-36Ra is the antagonist that is specific for IL-36α, β, γ and does this by binding to ILRrp2, in an analogous way to IL-1Ra inhibition of IL-1β. IL-36 signalling activates mitogen-activated protein kinases (MAPKs) and NF-KB resulting in downstream target gene activation. IL-36 signals through the IL-36 Receptor and its co-receptor IL1R accessory protein is necessary for downstream signalling. IL-36α functions primarily in skin and demonstrates increased expression in psoriasis. In addition, decreased expression of this protein has been linked to a poor prognosis in both hepatocellular carcinoma and colorectal cancer patients.
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