Functional IL-1 signaling requires IL-1R1 and IL-1-dependent recruitment of IL-1RAP. Membrane bound IL-1R2 serves as a negative regulator of IL-1 by competing with IL-1R1 for IL-1 and by complexing with IL-1RAP which prevents IL-1RAP from heterodimerizing with IL-1R1. IL-1 can also interact with sIL-1R2 and the sIL-1R2 + sIL-1RAP complex. The sIL-1R2 + sIL-1RAP complex has a greater affinity for IL-1 than sIL-lR2 or IL-1R2, alone. Finally, the processing of pro-IL-1β to mature IL-1β by caspase-1 can be prevented by the binding of pro-IL-1β to intracellular sIL-1R2. Abbreviations: IL-1 receptor type 1 (IL-1R1), IL-1 receptor type 2 (IL-1R2), soluble IL-1R2 (sIL-1R2), IL-1 receptor accessory protein (IL-1RAP).