Hepcidin as a predictive factor and therapeutic target in erythropoiesis-stimulating agent treatment for anemia of chronic disease in rats

Haematologica

Volumn 99, Issue 9, 2014, Pages 1516-1524

  Theurl, Milan ^a   Nairz, Manfred ^a   Schroll, Andrea ^a   Sonnweber, Thomas ^a   Asshoff, Malte ^a   Haschka, David ^a   Seifert, Markus ^a   Willenbacher, Wolfgang ^a   Wilflingseder, Doris ^a   Posch, Wilfried ^a   Murphy, Anthony T ^b   Witcher, Derrick R ^b   Theurl, Igor ^a   Weiss, Günter ^a  

^a INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^b ELI LILLY AND COMPANY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIANEMIC AGENT; CYTOKINE; ERYTHROPOIETIN; FP1 PROTEIN; HEMOGLOBIN; HEPCIDIN; IRON; LDN; LDN 193189; MESSENGER RNA; NOVEL ERYTHROPOIESIS STIMULATING PROTEIN; PROTEIN; RECOMBINANT ERYTHROPOIETIN; RHEPO; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; 6 [4 (1 PIPERAZINYL)PHENYL] 3 (4 QUINOLINYL)PYRAZOLO[1,5 A]PYRIMIDINE; BACTERIAL POLYSACCHARIDE; BIOLOGICAL MARKER; DRUG COMBINATION; GAMMA INTERFERON; HAMP PROTEIN, RAT; PYRAZOLE DERIVATIVE; PYRIMIDINE DERIVATIVE;

ANEMIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOLOGICAL ACTIVITY; CONTROLLED STUDY; DRUG EFFICACY; ERYTHROPOIESIS; FEMALE; FLOW CYTOMETRY; FLUORESCENCE ACTIVATED CELL SORTING; HEMOSTASIS; IMMUNOFLUORESCENCE; INFLAMMATION; MEAN CORPUSCULAR VOLUME; MONOTHERAPY; NONHUMAN; PATHOGENESIS; PROTEIN EXPRESSION; RAT; REAL TIME POLYMERASE CHAIN REACTION; RETICULOENDOTHELIAL SYSTEM; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; WESTERN BLOTTING; AGONISTS; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOSYNTHESIS; BLOOD; CHEMICALLY INDUCED; CHRONIC DISEASE; DRUG COMBINATION; DRUG EFFECTS; DRUG POTENTIATION; GENE EXPRESSION; GENETICS; HUMAN; LEWIS RAT; PATHOLOGY; PROGNOSIS;

ANEMIA; ANIMALS; BIOLOGICAL MARKERS; CHRONIC DISEASE; DRUG COMBINATIONS; DRUG SYNERGISM; ERYTHROPOIESIS; ERYTHROPOIETIN; FEMALE; GENE EXPRESSION; HEMATINICS; HEPCIDINS; HUMANS; INTERFERON-GAMMA; IRON; POLYSACCHARIDES, BACTERIAL; PROGNOSIS; PYRAZOLES; PYRIMIDINES; RATS; RATS, INBRED LEW; RNA, MESSENGER; TUMOR NECROSIS FACTOR-ALPHA;

EID: 84907378165     PISSN: 03906078     EISSN: 15928721     Source Type: Journal    
DOI: 10.3324/haematol.2013.099481     Document Type: Article

References (50)

1. Matzner Y, Levy S, Grossowicz N, Izak G, Hershko C. Prevalence and causes of anemia in elderly hospitalized patients. Gerontology. 1979;25(2):113-119.
2. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10): 1011-1023.
3. Ganz T, Nemeth E. Iron sequestration and anemia of inflammation. Semin Hematol. 2009;46(4):387-393.
4. Weiss G, Schett G. Anaemia in inflammatory rheumatic diseases. Nat Rev Rheumatol. 2013;9(4):205-215.
5. Babitt JL, Lin HY. Mechanisms of Anemia in CKD. J Am Soc Nephrol. 2012;23(10): 1631-1634.
6. Pantopoulos K, Porwal SK, Tartakoff A, Devireddy L. Mechanisms of mammalian iron homeostasis. Biochemistry (Mosc). 2012;51(29):5705-5724.
7. Theurl I, Aigner E, Theurl M, Nairz M, Seifert M, Schroll A, et al. Regulation of iron homeostasis in anemia of chronic disease and iron deficiency anemia: diagnostic and therapeutic implications. Blood. 2009;113 (21):5277-5286.
8. Ludwiczek S, Aigner E, Theurl I, Weiss G. Cytokine-mediated regulation of iron transport in human monocytic cells. Blood. 2003;101(10):4148-4154.
9. Theurl I, Mattle V, Seifert M, Mariani M, Marth C, Weiss G. Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease. Blood. 2006;107(10):4142-4148.
10. Roy CN, Mak HH, Akpan I, Losyev G, Zurakowski D, Andrews NC. Hepcidin antimicrobial peptide transgenic mice exhibit features of the anemia of inflammation. Blood. 2007;109(9):4038-4044.
11. Means RT Jr. Recent developments in the anemia of chronic disease. Curr Hematol Rep. 2003;2(2):116-121.
12. Cazzola M, Ponchio L, de Benedetti F, Ravelli A, Rosti V, Beguin Y, 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 (11):4824-4830.
13. Jelkmann W. Regulation of erythropoietin production. J Physiol. 2011;589(6):1251-1258.
14. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. science. 2004;306(5704):2090-2093.
15. Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, et al. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest. 2002;110(7):1037-1044.
16. Kemna E, Pickkers P, Nemeth E, van der Hoeven H, Swinkels D. Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS. Blood. 2005;106(5):1864-1866.
17. Hentze MW, Muckenthaler MU, Galy B, Camaschella C. Two to tango: regulation of mammalian iron metabolism. Cell. 2010;142 (1):24-38.
18. Schwoebel F, van Eijk LT, Zboralski D, Sell S, Buchner K, Maasch C, et al. The effects of the anti-hepcidin Spiegelmer NOX-H94 on inflammation-induced anemia in cynomol-gus monkeys. Blood. 2013;121(12):2311-2315.
19. Sasu BJ, Cooke KS, Arvedson TL, Plewa C, Ellison AR, Sheng J, et al. Antihepcidin antibody treatment modulates iron metabolism and is effective in a mouse model of inflammation-induced anemia. Blood. 2010;115 (17):3616-3624.
20. Steinbicker AU, Sachidanandan C, Vonner AJ, Yusuf RZ, Deng DY, Lai CS, et al. Inhibition of bone morphogenetic protein signaling attenuates anemia associated with inflammation. Blood. 2011;117(18): 4915-4923.
21. Theurl I, Schroll A, Sonnweber T, Nairz M, Theurl M, Willenbacher W, et al. Pharmacologic inhibition of hepcidin expression reverses anemia of chronic inflammation in rats. Blood. 2011;118(18): 4977-4984.
22. Kroot JJC, Tjalsma H, Fleming RE, Swinkels DW. Hepcidin in human iron disorders: diagnostic implications. Clin Chem. 2011;57 (12):1650-1669.
23. Rivera S, Nemeth E, Gabayan V, Lopez MA, Farshidi D, Ganz T. Synthetic hepcidin causes rapid dose-dependent hypoferremia and is concentrated in ferroportin-containing organs. Blood. 2005;106(6):2196-2199.
24. Nicolas G, Viatte L, Bennoun M, Beaumont C, Kahn A, Vaulont S. Hepcidin, a new iron regulatory peptide. Blood Cells Mol Dis. 2002;29(3):327-335.
25. Liu Q, Davidoff O, Niss K, Haase VH. Hypoxia-inducible factor regulates hepcidin via erythropoietin-induced erythropoiesis. J Clin Invest. 2012;122(12):4635-4644.
26. Sasaki Y, Noguchi-Sasaki M, Yasuno H, Yorozu K, Shimonaka Y. Erythropoietin stimulation decreases hepcidin expression through hematopoietic activity on bone marrow cells in mice. Int J Hematol. 2012;96(6):692-700.
27. Lasocki S, Millot S, Andrieu V, Lettéron P, Pilard N, Muzeau F, et al. Phlebotomies or erythropoietin injections allow mobilization of iron stores in a mouse model mimicking intensive care anemia. Crit Care Med. 2008;36(8):2388-2394.
28. Millot S, Andrieu V, Letteron P, Lyoumi S, Hurtado-Nedelec M, Karim Z, et al. Erythropoietin stimulates spleen BMP4-dependent stress erythropoiesis and partially corrects anemia in a mouse model of generalized inflammation. Blood. 2010;116(26): 6072-6081.
29. Littlewood TJ, Bajetta E, Nortier JWR, Vercammen E, Rapoport B. Effects of epoet-in alfa on hematologic parameters and quality of life in cancer patients receiving non-platinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2001;19(11):2865-2874.
30. Spivak JL, Gascón P, Ludwig H. Anemia management in oncology and hematology. Oncologist. 2009;14(Suppl 1):43-56.
31. Pfeffer MA, Burdmann EA, Chen C-Y, Cooper ME, de Zeeuw D, Eckardt K-U, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med. 2009;361(21):2019-2032.
32. Bohlius J, Schmidlin K, Brillant C, Schwarzer G, Trelle S, Seidenfeld J, et al. Recombinant human erythropoiesis-stimulating agents and mortality in patients with cancer: a meta-analysis of randomised trials. Lancet. 2009;373(9674):1532-1542.
33. Solomon SD, Uno H, Lewis E F, Eckardt K-U, Lin J, Burdmann EA, et al. Erythropoietic response and outcomes in kidney disease and type 2 diabetes. N Engl J Med. 2010;363(12):1146-1155.
34. Goodnough LT, Nemeth E, Ganz T. Detection, evaluation, and management of iron-restricted erythropoiesis. Blood. 2010;116(23):4754-4761.
35. Coccia MA, Cooke K, Stoney G, Pistillo J, Del Castillo J, Duryea D, et al. Novel ery-thropoiesis stimulating protein (darbepoetin alfa) alleviates anemia associated with chronic inflammatory disease in a rodent model. Exp Hematol. 2001;29(10):1201-1209.
36. Ludwiczek S, Theurl I, Muckenthaler MU, Jakab M, Mair SM, Theurl M, et al. Ca2+ channel blockers reverse iron overload by a new mechanism via divalent metal trans-porter-1. Nat Med. 2007;13(4):448-454.
37. Theurl M, Theurl I, Hochegger K, Obrist P, Subramaniam N, van Rooijen N, et al. Kupffer cells modulate iron homeostasis in mice via regulation of hepcidin expression. J Mol Med. 2008;86(7):825-835.
38. Richardson CL, Delehanty LL, Bullock GC, Rival CM, Tung KS, Kimpel DL, et al. Isocitrate ameliorates anemia by suppressing the erythroid iron restriction response. J Clin Invest. 2013;123(8):3614-3623.
39. Nairz M, Schroll A, Moschen AR, Sonnweber T, Theurl M, Theurl I, et al. Erythropoietin contrastingly affects bacterial infection and experimental colitis by inhibiting nuclear factor-κB-inducible immune pathways. Immunity. 2011;34(1): 61-74.
40. De Domenico I, Zhang TY, Koening CL, Branch RW, London N, Lo E, et al. Hepcidin mediates transcriptional changes that modulate acute cytokine-induced inflammatory responses in mice. J Clin Invest. 2010;120(7): 2395-2405.
41. Pagani A, Nai A, Corna G, Bosurgi L, Rovere-Querini P, Camaschella C, et al. Low hepcidin accounts for the proinflammatory status associated with iron deficiency. Blood. 2011;118(3):736-746.
42. Delaby C, Pilard N, Puy H, Canonne-Hergaux F. Sequential regulation of ferro-portin expression after erythrophagocytosis in murine macrophages: early mRNA induction by haem, followed by iron-dependent protein expression. Biochem J. 2008;411(1): 123-131.
43. Knutson MD, Oukka M, Koss LM, Aydemir F, Wessling-Resnick M. Iron release from macrophages after erythrophagocytosis is up-regulated by ferroportin 1 overexpres-sion and down-regulated by hepcidin. Proc Natl Acad Sci USA. 2005;102(5):1324-1328.
44. Soe-Lin S, Apte SS, Andriopoulos B, Andrews MC, Schranzhofer M, Kahawita T, et al. Nramp1 promotes efficient macrophage recycling of iron following ery-throphagocytosis in vivo. Proc Natl Acad Sci USA. 2009;106(14):5960-5965.
45. Prentice AM, Doherty CP, Abrams SA, Cox SE, Atkinson SH, Verhoef H, et al. Hepcidin is the major predictor of erythrocyte iron incorporation in anemic African children. Blood. 2012;119(8):1922-8.
46. Theurl I, Schroll A, Nairz M, Seifert M, Theurl M, Sonnweber T, et al. Pathways for the regulation of hepcidin expression in anemia of chronic disease and iron deficiency anemia in vivo. Haematologica. 2011;96(12): 1761-1769.
47. Mast AE, Schlumpf KS, Wright DJ, Johnson B, Glynn SA, Busch MP, et al. Hepcidin level predicts hemoglobin concentration in individuals undergoing repeated phlebotomy. Haematologica. 2013;98(8):1324-1330.
48. Tanno T, Bhanu NV, Oneal PA, Goh S-H, Staker P, Lee YT, et al. High levels of GDF15 in thalassemia suppress expression of the iron regulatory protein hepcidin. Nat Med. 2007;13(9):1096-1101.
49. Yamaji S, Sharp P, Ramesh B, Srai SK. Inhibition of iron transport across human intestinal epithelial cells by hepcidin. Blood. 2004;104(7):2178-2180.
50. Libregts SF, Gutiérrez L, de Bruin AM, Wensveen FM, Papadopoulos P, van Ijcken W, 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(9): 2578-2588.