4-Octyl Itaconate is a cell-permeable derivative of itaconate, a metabolite produced during the Krebs cycle. It is a potent activator of nuclear factor erythroid 2-related factor 2 (Nrf2) via alkylation of the inhibitor of Nrf2 (Keap1), thereby promoting Nrf2-mediated transcriptional activation and downstream anti-oxidant and anti-inflammatory properties (Mills et al.; Tang et al.).


IMMUNOLOGY
· The itaconate pathway (IRG1-itaconate-SDH) plays a pivotal role in up-regulating tolerance and inhibiting the induction of trained immunity (Domínguez-Andrés et al.).
· Counteracts the proinflammatory signals of succinate by inhibiting succinate dehydrogenase (SDH) and activating Nrf2 to limit inflammation in mouse and human macrophages (Lampropoulou et al.; Mills et al.).
· Activates Nrf2 signaling in human macrophages, which has been shown to inhibit the production of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6 (Tang et al.).