Potential therapeutic targets on the IL-1 pathway and available IL-1–targeting therapies. Production of IL-1β, mainly by monocytes, macrophages, and dendritic cells, requires a stimulus such as MAMPs or DAMPs. IL-1α does not require a stimulus, and is released upon cell necrosis (bottom panel). IL-1α and IL-1β bind to the IL-1R1 and induce further intracellular signaling pathways, whereas IL-1R2 functions as a decoy receptor for IL-1. Various agents are available that target specific components of the IL-1 pathway. rhIL-1Ra anakinra targets both IL-1α and IL-1β, as does the sIL-1R rilonacept. Specific antibodies targeting IL-1α or IL-1β are MABp1 and canakinumab, respectively. Both IL1RAP, a coreceptor of the IL-1R1, and IRAK1, a kinase downstream of the IL-1R1, have also been suggested potential targets for treatment of hematological malignancies. MyD88, myeloid differentiation primary response 88; rhIL-1Ra, recombinant human IL-1Ra; sIL-1R, soluble IL-1R; TRAF6, TNF receptor–associated factor 6.