IL-1 regulates a broad range of both immune and inflammatory responses and plays a critical role in autoinflammatory diseases. Although IL-1 activates NF-kB that regulates many IL-1 controlled processes, IL-1 also induces expression of transcription factor IRF1, yet the roles and mechanisms of its activation remain elusive. In contrast to TLRs that effectively activate IRF3 and IRF7 and induce chemokine production and efficient recruitment of mononuclear cells to sites of infection, we show that the recruitment of mononuclear cells to sites of sterile inflammation is coordinated by IL-1R-mediated activation of IRF1. We found that IRF1 is essential for IL-1-induced expression of the chemokines CXCL10 and CCL5 that in turn recruit mononuclear cells into sites of sterile inflammation. Newly synthesized IRF1 acquires K63-linked polyubiquitination mediated by cellular inhibitor of apoptosis 2 (cIAP2), whose E3 ligase activity is enhanced by the bioactive lipid sphingosine-1 phosphate (S1P). In response to IL-1, cIAP2 and sphingosine kinase 1, the enzyme that generates S1P, form a complex with IRF1, which leads to its activation. Thus, IL-1 triggers a novel signaling cascade that controls induction of IRF1-dependent genes important for sterile inflammation. Targeting of this newly discovered IL-1-induced cascade may be clinically important in the future.