Anemia of chronic disease pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2] Associate Editor(s)-in-Chief: Omer Kamal, M.D.[3]


Inflammatory cytokines induce increased amounts of hepcidin by the liver. Hepcidin blocks ferroportin from releasing iron from the body stores. Inflammatory cytokines also decrease ferroportin expression and stops erythropoiesis by increasing bone marrow erythropoietin resistance. Apart from iron sequestration, white blood cells production is promoted by inflammatory cytokines. Bone marrow stem cells produce both red blood cells and white blood cells cells. Therefore, the upregulation of white blood cells causes fewer stem cells to differentiate into red blood cells. This may also have a role in inhibition of erythropoiesis, even when erythropoietin levels are normal, and aside from the effects of hepcidin.



Activated monocytes release cytokines like the interleukins (eg, IL-1 and IL-6) and tumor necrosis factor (TNF-alpha). These cytokines activate a cascade of reactions leading to the secretion of interferon (IFN)-beta and IFN-gamma by T lymphocytes leading to increased resistance of bone marrow to EPO.[9][10]


Hepcidin is directly involved in iron metabolism and a component of the innate immune response to acute infection. It decreases the absorption of iron from small intestine, from placenta and from macrophages as well, secondary to its effect on internalization and degradation of the iron export protein ferroportin.[11][12][13][14]


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  2. Roy CN (2010). "Anemia of inflammation". Hematology Am Soc Hematol Educ Program. 2010: 276–80. doi:10.1182/asheducation-2010.1.276. PMID 21239806.
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  4. Means RT (July 1999). "Advances in the anemia of chronic disease". Int. J. Hematol. 70 (1): 7–12. PMID 10446488.
  5. 5.0 5.1 Theurl I, Mattle V, Seifert M, Mariani M, Marth C, Weiss G (May 2006). "Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease". Blood. 107 (10): 4142–8. doi:10.1182/blood-2005-08-3364. PMID 16434484.
  6. Papadaki HA, Kritikos HD, Gemetzi C, Koutala H, Marsh JC, Boumpas DT, Eliopoulos GD (March 2002). "Bone marrow progenitor cell reserve and function and stromal cell function are defective in rheumatoid arthritis: evidence for a tumor necrosis factor alpha-mediated effect". Blood. 99 (5): 1610–9. PMID 11861275.
  7. Papadaki HA, Kritikos HD, Valatas V, Boumpas DT, Eliopoulos GD (July 2002). "Anemia of chronic disease in rheumatoid arthritis is associated with increased apoptosis of bone marrow erythroid cells: improvement following anti-tumor necrosis factor-alpha antibody therapy". Blood. 100 (2): 474–82. doi:10.1182/blood-2002-01-0136. PMID 12091338.
  8. Weiss G, Goodnough LT (March 2005). "Anemia of chronic disease". N. Engl. J. Med. 352 (10): 1011–23. doi:10.1056/NEJMra041809. PMID 15758012.
  9. Boutou AK, Pitsiou GG, Stanopoulos I, Kontakiotis T, Kyriazis G, Argyropoulou P (July 2012). "Levels of inflammatory mediators in chronic obstructive pulmonary disease patients with anemia of chronic disease: a case-control study". QJM. 105 (7): 657–63. doi:10.1093/qjmed/hcs024. PMID 22355163.
  10. Raj DS (April 2009). "Role of interleukin-6 in the anemia of chronic disease". Semin. Arthritis Rheum. 38 (5): 382–8. doi:10.1016/j.semarthrit.2008.01.006. PMID 18336871.
  11. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T (April 2003). "Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein". Blood. 101 (7): 2461–3. doi:10.1182/blood-2002-10-3235. PMID 12433676.
  12. Armitage AE, Eddowes LA, Gileadi U, Cole S, Spottiswoode N, Selvakumar TA, Ho LP, Townsend AR, Drakesmith H (October 2011). "Hepcidin regulation by innate immune and infectious stimuli". Blood. 118 (15): 4129–39. doi:10.1182/blood-2011-04-351957. PMID 21873546.
  13. Ganz T (April 2011). "Hepcidin and iron regulation, 10 years later". Blood. 117 (17): 4425–33. doi:10.1182/blood-2011-01-258467. PMC 3099567. PMID 21346250.
  14. Drakesmith H, Prentice AM (November 2012). "Hepcidin and the iron-infection axis". Science. 338 (6108): 768–72. doi:10.1126/science.1224577. PMID 23139325.