Metabolic reprogramming during the activation of immune cells has become a fascinating area of immunology. These events are not only important for energy production and biosynthesis but are also critically important for determining the phenotype of the cell. Macrophages in particular show marked metabolic differences based on their function with inflammatory macrophages being highly glycolytic whilst anti-inflammatory macrophages have more oxidative metabolism. Krebs cycle in particular shows differences. In LPS-activated macrophages succinate accumulates and is oxidised by succinate dehydrogenase, generating Reactive oxygen species via reverse electron transport at Complex I in the electron transport chain. This leads to HIF activation and the induction of cytokines such as IL1beta. Another Krebs cycle - derived metabolite, itaconate, which is derived from citrate can inhibit this response but importantly we have found that itaconate is required for Nrf2 activation, promoting an overall anti-inflammatory response. Itaconate can also limit Type I interferon production. What is emerging therefore is a critical role for Krebs cycle intermediates in governing cytokines profiles. These findings may point to new therapeutic options for inflammatory diseases.