Anemia of inflammation

New England Journal of Medicine

Volumn 381, Issue 12, 2019, Pages 1148-1157

  Ganz, Tomas ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FERRITIN; HEMOGLOBIN; IRON; RECOMBINANT ERYTHROPOIETIN; TRANSFERRIN; TUMOR NECROSIS FACTOR INHIBITOR; BIOLOGICAL MARKER;

ADVERSE OUTCOME; ANEMIA; ANEMIA OF INFLAMMATION; BONE MARROW DISEASE; ERYTHROCYTE LIFESPAN; ERYTHROPOIESIS; FERRITIN BLOOD LEVEL; HEMATOLOGICAL PARAMETERS; HOST RESISTANCE; HUMAN; HYPOFERREMIA; INFLAMMATION; IRON DEFICIENCY ANEMIA; IRON METABOLISM; NONHUMAN; NORMOCHROMIC NORMOCYTIC ANEMIA; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; RHEUMATOID ARTHRITIS; TRANSFERRIN SATURATION; BLOOD; COMPLICATION; METABOLISM;

ANEMIA; BIOMARKERS; HEMOGLOBINS; HUMANS; INFLAMMATION; IRON;

EID: 85072374277     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMra1804281     Document Type: Review

References (71)

1. Cartwright GE. The anemia of chronic disorders. Semin Hematol 1966;3:351-75.
2. Thomas J, Jensen L, Nahirniak S, Gibney RTN. Anemia and blood transfusion practices in the critically ill: a prospective cohort review. Heart Lung 2010;39:217-25.
3. Scharte M, Fink MP. Red blood cell physiology in critical illness. Crit Care Med 2003;31:Suppl:S651-S657.
4. Corwin HL, Krantz SB. Anemia of the critically ill: “acute” anemia of chronic disease. Crit Care Med 2000;28:3098-9.
5. Shaw JG, Friedman JF. Iron deficiency anemia: focus on infectious diseases in lesser developed countries. Anemia 2011; 2011:260380.
6. Hanudel MR, Chua K, Rappaport M, et al. Effects of dietary iron intake and chronic kidney disease on fibroblast growth factor 23 metabolism in wild-type and hepcidin knockout mice. Am J Physiol Renal Physiol 2016;311:F1369-F1377.
7. Opasich C, Cazzola M, Scelsi L, et al. Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure. Eur Heart J 2005;26: 2232-7.
8. Boutou AK, Hopkinson NS, Polkey MI. Anaemia in chronic obstructive pulmonary disease: an insight into its prevalence and pathophysiology. Clin Sci (Lond) 2015;128:283-95.
9. Fischer R, Simmerlein R, Huber RM, Schiffl H, Lang SM. Lung disease severity, chronic inflammation, iron deficiency, and erythropoietin response in adults with cystic fibrosis. Pediatr Pulmonol 2007;42: 1193-7.
10. Stauder R, Valent P, Theurl I. Anemia at older age: etiologies, clinical implications, and management. Blood 2018;131: 505-14.
11. Ganz T. Systemic iron homeostasis. Physiol Rev 2013;93:1721-41.
12. Wang CY, Babitt JL. Liver iron sensing and body iron homeostasis. Blood 2019; 133:18-29.
13. Roth MP, Meynard D, Coppin H. Regulators of hepcidin expression. Vitam Horm 2019;110:101-29.
14. Nemeth E, Rivera S, Gabayan V, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 2004;113:1271-6.
15. Tussing-Humphreys LM, Nemeth E, Fantuzzi G, et al. Elevated systemic hepcidin and iron depletion in obese premenopausal females. Obesity (Silver Spring) 2010;18:1449-56.
16. Li H, Rose MJ, Tran L, et al. Development of a method for the sensitive and quantitative determination of hepcidin in human serum using LC-MS/MS. J Pharmacol Toxicol Methods 2009;59:171-80.
17. Orkin SH. Diversification of haematopoietic stem cells to specific lineages. Nat Rev Genet 2000;1:57-64.
18. Dzierzak E, Philipsen S. Erythropoiesis: development and differentiation. Cold Spring Harb Perspect Med 2013;3(4): a011601.
19. Dulmovits BM, Hom J, Narla A, Mohandas N, Blanc L. Characterization, regulation, and targeting of erythroid progenitors in normal and disordered human erythropoiesis. Curr Opin Hematol 2017; 24:159-66.
20. Khalil S, Delehanty L, Grado S, et al. Iron modulation of erythropoiesis is associated with Scribble-mediated control of the erythropoietin receptor. J Exp Med 2018;215:661-79.
21. Suragani RN, Cadena SM, Cawley SM, et al. Transforming growth factor-β superfamily ligand trap ACE-536 corrects anemia by promoting late-stage erythropoiesis. Nat Med 2014;20:408-14.
22. Stefanova D, Raychev A, Deville J, et al. Hepcidin protects against lethal Escherichia coli sepsis in mice inoculated with isolates from septic patients. Infect Immun 2018;86(7):e00253-18.
23. Stefanova D, Raychev A, Arezes J, et al. Endogenous hepcidin and its agonist mediate resistance to selected infections by clearing non-transferrin-bound iron. Blood 2017;130:245-57.
24. Truman-Rosentsvit M, Berenbaum D, Spektor L, et al. Ferritin is secreted via 2 distinct nonclassical vesicular pathways. Blood 2018;131:342-52.
25. Bullock GC, Delehanty LL, Talbot AL, et al. Iron control of erythroid development by a novel aconitase-associated regulatory pathway. Blood 2010;116:97-108.
26. Han AP, Yu C, Lu L, et al. Heme-regulated eIF2alpha kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. EMBO J 2001;20:6909-18.
27. Orsini M, Chateauvieux S, Rhim J, et al. Sphingolipid-mediated inflammatory signaling leading to autophagy inhibition converts erythropoiesis to myelopoiesis in human hematopoietic stem/progenitor cells. Cell Death Differ 2019;26:1796-812.
28. Libregts SF, Gutiérrez L, de Bruin AM, et al. Chronic IFN-γ production in mice induces anemia by reducing erythrocyte life span and inhibiting erythropoiesis through an IRF-1/PU.1 axis. Blood 2011; 118:2578-88.
29. Means RT Jr, Dessypris EN, Krantz SB. Inhibition of human erythroid colony-forming units by interleukin-1 is mediated by gamma interferon. J Cell Physiol 1992; 150:59-64.
30. Means RT Jr, Krantz SB. Inhibition of human erythroid colony-forming units by gamma interferon can be corrected by recombinant human erythropoietin. Blood 1991;78:2564-7.
31. Miller CB, Jones RJ, Piantadosi S, Abeloff MD, Spivak JL. Decreased erythropoietin response in patients with the anemia of cancer. N Engl J Med 1990;322: 1689-92.
32. Cazzola M, Ponchio L, de Benedetti F, et al. Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis. Blood 1996;87:4824-30.
33. Souma T, Yamazaki S, Moriguchi T, et al. Plasticity of renal erythropoietin-producing cells governs fibrosis. J Am Soc Nephrol 2013;24:1599-616.
34. Macdougall IC, Cooper AC. Erythropoietin resistance: the role of inflammation and pro-inflammatory cytokines. Nephrol Dial Transplant 2002;17:Suppl 11: 39-43.
35. Kimachi M, Fukuma S, Yamazaki S, et al. Minor elevation in C-reactive protein levels predicts incidence of erythropoiesis-stimulating agent hyporesponsiveness among hemodialysis patients. Nephron 2015;131:123-30.
36. Cavill I, Bentley DP. Erythropoiesis in the anaemia of rheumatoid arthritis. Br J Haematol 1982;50:583-90.
37. Mitlyng BL, Singh JA, Furne JK, Ruddy J, Levitt MD. Use of breath carbon monoxide measurements to assess erythrocyte survival in subjects with chronic diseases. Am J Hematol 2006;81:432-8.
38. Kim A, Fung E, Parikh SG, et al. A mouse model of anemia of inflammation: complex pathogenesis with partial dependence on hepcidin. Blood 2014;123:1129-36.
39. Zoller EE, Lykens JE, Terrell CE, et al. Hemophagocytosis causes a consumptive anemia of inflammation. J Exp Med 2011; 208:1203-14.
40. Petzer V, Theurl I, Weiss G. Established and emerging concepts to treat imbalances of iron homeostasis in inflammatory diseases. Pharmaceuticals (Basel) 2018;11:135.
41. Thomason RW, Lavelle J, Nelson D, Lin K, Uherova P. Parenteral iron therapy is associated with a characteristic pattern of iron staining on bone marrow aspirate smears. Am J Clin Pathol 2007;128:590-3.
42. Barron BA, Hoyer JD, Tefferi A. A bone marrow report of absent stainable iron is not diagnostic of iron deficiency. Ann Hematol 2001;80:166-9.
43. Krause JR, Brubaker D, Kaplan S. Comparison of stainable iron in aspirated and needle-biopsy specimens of bone marrow. Am J Clin Pathol 1979;72:68-70.
44. Weber J, Werre JM, Julius HW, Marx JJ. Decreased iron absorption in patients with active rheumatoid arthritis, with and without iron deficiency. Ann Rheum Dis 1988;47:404-9.
45. Stoffel NU, Lazrak M, Bellitir S, et al. The opposing effects of acute inflammation and iron deficiency anemia on serum hepcidin and iron absorption in young women. Haematologica 2019;104:1143-9.
46. Auerbach M, Macdougall I. The available intravenous iron formulations: history, efficacy, and toxicology. Hemodial Int 2017;21:Suppl 1:S83-S92.
47. Belotti A, Duca L, Borin L, et al. Non transferrin bound iron (NTBI) in acute leukemias throughout conventional intensive chemotherapy: kinetics of its appearance and potential predictive role in infectious complications. Leuk Res 2015;39: 88-91.
48. Sazawal S, Black RE, Ramsan M, et al. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. Lancet 2006;367:133-43.
49. Song S-NJ, Tomosugi N, Kawabata H, Ishikawa T, Nishikawa T, Yoshizaki K. Down-regulation of hepcidin resulting from long-term treatment with an anti-IL-6 receptor antibody (tocilizumab) improves anemia of inflammation in multicentric Castleman disease. Blood 2010; 116:3627-34.
50. Weiss LM, Gonzalez E, Miller SB, Agudelo CA. Severe anemia as the presenting manifestation of giant cell arteritis. Arthritis Rheum 1995;38:434-6.
51. Song S-NJ, Iwahashi M, Tomosugi N, et al. Comparative evaluation of the effects of treatment with tocilizumab and TNF-α inhibitors on serum hepcidin, anemia response and disease activity in rheumatoid arthritis patients. Arthritis Res Ther 2013; 15:R141.
52. Gil-Santana L, Cruz LAB, Arriaga MB, et al. Tuberculosis-associated anemia is linked to a distinct inflammatory profile that persists after initiation of antitubercular therapy. Sci Rep 2019;9:1381.
53. Hedenus M, Birgegård G. The role of iron supplementation during epoietin treatment for cancer-related anemia. Med Oncol 2009;26:105-15.
54. Cody JD, Hodson EM. Recombinant human erythropoietin versus placebo or no treatment for the anaemia of chronic kidney disease in people not requiring dialysis. Cochrane Database Syst Rev 2016; 1:CD003266.
55. Fishbane S, Ross DW, Hong S. Anemia in non-dialysis-dependent CKD: to treat or not to treat? Am J Kidney Dis 2019;73:297-9.
56. Martí-Carvajal AJ, Agreda-Pérez LH, Solà I, Simancas-Racines D. Erythropoiesis-stimulating agents for anemia in rheumatoid arthritis. Cochrane Database Syst Rev 2013;2:CD000332.
57. Poli M, Asperti M, Ruzzenenti P, et al. Oversulfated heparins with low anticoagulant activity are strong and fast inhibitors of hepcidin expression in vitro and in vivo. Biochem Pharmacol 2014;92:467-75.
58. Theurl I, Schroll A, Sonnweber T, et al. Pharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats. Blood 2011;118:4977-84.
59. Hohlbaum AM, Gille H, Trentmann S, et al. Sustained plasma hepcidin suppression and iron elevation by Anticalinderived hepcidin antagonist in cynomolgus monkey. Br J Pharmacol 2018;175: 1054-65.
60. Boyce M, Warrington S, Cortezi B, et al. Safety, pharmacokinetics and pharmacodynamics of the anti-hepcidin Spiegelmer lexaptepid pegol in healthy subjects. Br J Pharmacol 2016;173:1580-8.
61. Sheetz M, Barrington P, Callies S, et al. Targeting the hepcidin-ferroportin pathway in anaemia of chronic kidney disease. Br J Clin Pharmacol 2019;85:935-48.
62. Vadhan-Raj S, Abonour R, Goldman JW, et al. A first-in-human phase 1 study of a hepcidin monoclonal antibody, LY2787106, in cancer-associated anemia. J Hematol Oncol 2017;10:73.
63. Sasu BJ, Cooke KS, Arvedson TL, et al. Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia. Blood 2010;115:3616-24.
64. Kovac S, Böser P, Cui Y, et al. Anti-hemojuvelin antibody corrects anemia caused by inappropriately high hepcidin levels. Haematologica 2016;101(5):e173-e176.
65. Asshoff M, Petzer V, Warr MR, et al. Momelotinib inhibits ACVR1/ALK2, decreases hepcidin production, and ameliorates anemia of chronic disease in rodents. Blood 2017;129:1823-30.
66. Mesa RA, Kiladjian JJ, Catalano JV, et al. SIMPLIFY-1: a phase III randomized trial of momelotinib versus ruxolitinib in Janus kinase inhibitor-naïve patients with myelofibrosis. J Clin Oncol 2017;35:3844-50.
67. Peterson P, Whatcott CJ, et al. TP-0184 inhibits ALK2/ACVR1, decreases hepcidin levels, and demonstrates activity in preclinical mouse models of functional iron deficiency. Blood 2017;130:Suppl 1:937. abstract.
68. Barrett TD, Palomino HL, Brondstetter TI, et al. Prolyl hydroxylase inhibition corrects functional iron deficiency and inflammation-induced anaemia in rats. Br J Pharmacol 2015;172:4078-88.
69. Chen N, Qian J, Chen J, et al. Phase 2 studies of oral hypoxia-inducible factor prolyl hydroxylase inhibitor FG-4592 for treatment of anemia in China. Nephrol Dial Transplant 2017;32:1373-86.
70. Wouters HJCM, van der Klauw MM, de Witte T, et al. Association of anemia with health-related quality of life and survival: a large population-based cohort study. Haematologica 2019;104:468-76.
71. Girelli D, Busti F. Anemia and adverse outcomes in the elderly: a detrimental inflammatory loop? Haematologica 2019; 104:417-9.