Iron deficiency controls the inflammatory response through modulation of hepcidin. Schematic representation of the proposed model. In normal conditions (iron balance; A), LPS, on binding TLR4, stimulates macrophages to produce inflammatory cytokines (IL6); hepcidin is up-regulated by STAT3 and released into the blood stream to control both iron recycling (not shown) and IL6 transcription in macrophages. In iron deficiency (B), hepcidin transcription is severely reduced. LPS injection activates macrophages to produce IL6. The IL6 production is exaggerated because of the lack of the hepcidin-mediated anti-inflammatory response. BMR-RE indicates bone morphogenetic protein–responsive element; STAT-RS, STAT3–responsive site; HAMP, hepcidin; FPN, Ferroportin; and TLR4, Toll-like Receptor 4.