Figure 1: In inflammatory diseases, cytokines released by activated leukocytes and other cells exert multiple effects that contribute to the reduction in hemoglobin levels: (A) Induction of hepcidin synthesis in the liver (especially by interleukin-6 [IL-6], along with endotoxin). Hepcidin in turn binds to ferroportin, the pore that allows egress of iron from reticuloendothelial macrophages and from intestinal epithelial cells. Binding of hepcidin leads to internalization and degradation of ferroportin; the corresponding sequestration of iron within the macrophages limits iron availability to erythroid precursors. (B) Inhibition of erythropoietin release from the kidney (especially by interleukin-1β [IL-1β] and tumour necrosis factor α [TNFα]). Erythropoietin-stimulated hematopoietic proliferation is in turn reduced. (C) Direct inhibition of the proliferation of erythroid progenitors (especially by TNFα, interferon-γ [IFNγ] and IL-1β). (D) Augmentation of erythrophagocytosis by reticuloendothelial macrophages (by TNFα). RES = reticuloendothelial system.. Image by: Lianne Friesen and Nicholas Woolridge