The IL-1 and IL-36 cytokine systems are extremely similar. IL-36 includes 3 functionally equivalent agonist cytokines, IL-36α, IL-36β, and IL-36γ, that interact with their own unique receptor IL-36 (formerly known as IL-1Rrp2), in the same way that the IL-1 agonists IL-1α and IL-1β interact with their unique signal-transducing receptor (IL-1R1). Alternatively, IL-36R can interact with a homologous antagonist molecule IL-36Ra in the same way that IL-1R1 interacts with the IL-1Ra. All of the agonist-receptor complexes interact with the same second receptor component, IL-1RAcP. Both receptor and antagonist complexes fail to associate with IL-1RAcP. Control of the expression of the ligands, their receptors, and their antagonists on different cells and at different times is likely to explain their differential functions.