A 55-year-old man with rheumatoid arthritis has Hb 10 g/dL, MCV 78 fL, serum ferritin 180 ng/mL, and low serum iron with low transferrin saturation. Bone marrow iron stains show abundant iron in macrophages but absent sideroblasts. Which mediator is primarily responsible for restricting iron availability in this condition?

• A Tumor necrosis factor induced apoptosis of duodenal enterocytes
• B Erythropoietin induced hypoxia inducible factor, which suppresses transferrin synthesis
• C Interleukin-6 induced hepcidin, which blocks ferroportin-mediated iron export ✓
• D Gamma interferon induced downregulation of divalent metal transporter 1 on enterocytes

Explanation

Anemia of chronic disease is driven by inflammatory cytokines, chiefly interleukin-6, which stimulates hepatic hepcidin release. Hepcidin binds ferroportin on macrophages and enterocytes, triggering its internalization and degradation, so absorbed and recycled iron becomes trapped in macrophage stores. This explains high marrow macrophage iron with no iron entering erythroid precursors. The abundant ferritin and absent sideroblasts distinguish it clearly from iron deficiency and sideroblastic anemia respectively.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.