Following the activation of several types of immune cells, cellular metabolism switches from oxidative phosphorylation to glycolysis. Now, Tannahill et al. report that in macrophages, stimulation of Toll-like receptor 4 by lipopolysaccharide (LPS) promotes such a metabolic switch and leads to the accumulation of succinate downstream of glutamine metabolism and the GABA (γ-aminobutyric acid) shunt. Succinate stabilized hypoxia-inducible factor 1α, which, in turn, promoted transcription of interleukin-1β (IL-1β). Notably, knockdown of a glutamine transporter or inhibition of the GABA shunt decreased the levels of LPS-induced IL-1β in vitro. Moreover, the GABA shunt inhibitor vigabatrin was protective in a mouse model of sepsis. Thus, metabolic signals such as succinate can promote inflammation.