A 60-year-old woman with rheumatoid arthritis has Hb 10 g/dL, MCV 78 fL. Serum iron is low, TIBC is low, transferrin saturation is 14%, and ferritin is 180 ng/mL. Which mediator accounts for the restricted iron availability in this condition?

• A Interferon-gamma downregulating transferrin receptor 2 in hepatocytes
• B Tumor necrosis factor suppressing erythropoietin receptors
• C Interleukin-1 blocking ALA synthase activity
• D Interleukin-6 induced hepcidin causing ferroportin internalization ✓

Explanation

Anemia of chronic disease is driven by IL-6 stimulating hepatic hepcidin release. Hepcidin binds ferroportin on enterocytes and macrophages, triggering its internalization and degradation, trapping iron in stores despite adequate total body iron. This explains the combination of low serum iron with normal to high ferritin and low TIBC, the profile that separates it from true iron deficiency where TIBC is high and ferritin low. TNF contributes to blunted EPO response but is not the central mediator.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

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