Model of the erythroblastic island during an inflammatory response. Itaconate is produced via IRG1 in immunoactivated blood island macrophages and excreted to the surrounding milieu. Subsequent import and metabolism of itaconate to itaconyl-CoA by proximal red cell precursors result in inhibition of ALA synthesis and cellular hemoglobinization at the point of ALAS2 catalysis. Interleukin 6 (IL6), tumor necrosis factor-α (TNFα), and interleukin 1β (IL1β) are proinflammatory cytokines. GSH, glutathione; IFNGR, interferon-γ (IFNγ) receptor; TLR4, Toll-like receptor 4.