Seminars in Hematology
Volume 46, Issue 4 , Pages 351-357 , October 2009

Animal Models of Anemia of Inflammation

  • Seth Rivera

      Affiliations

    • Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, CA
    • Corresponding Author InformationAddress correspondence to Seth Rivera, MD, PhD, Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, 10833 Le Conte Ave, 37-131 CHS, Los Angeles, CA 90095
    • ,
  • Tomas Ganz

      Affiliations

    • Department of Medicine, David Geffen School of Medicine at the University of California, Los Angeles, CA
    • Department of Pathology, David Geffen School of Medicine at the University of California, Los Angeles, CA

References 

  1. Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC. Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood. 2002;100:3776–3781
  2. 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;109:4038–4044
  3. Rivera S, Liu L, Nemeth E, Gabayan V, Sorensen OE, Ganz T. Hepcidin excess induces the sequestration of iron and exacerbates tumor-associated anemia. Blood. 2005;105:1797–1802
  4. Nguyen BV, Bota DP, Melot C, Vincent JL. Time course of hemoglobin concentrations in nonbleeding intensive care unit patients. Crit Care Med. 2003;31:406–410
  5. Vincent JL, Baron JF, Reinhart K, Gattinoni L, Thijs L, Webb A, et al. Anemia and blood transfusion in critically ill patients. JAMA. 2002;288:1499–1507
  6. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352:1011–1023
  7. Weiss G. Pathogenesis and treatment of anaemia of chronic disease. Blood Rev. 2002;16:87–96
  8. Anosa VO. Postsplenectomy blood values, marrow cytology, erythrocyte life-span, and sequestration in mice. Am J Physiol. 1976;231:1254–1257
  9. Wallner SF, Vautrin R, Katz J. The haematopoietic response to burning: studies in a splenectomized animal model. Burns Incl Therm Inj. 1987;13:15–21
  10. Schubert TE, Obermaier F, Ugocsai P, Mannel DN, Echtenacher B, Hofstadter F, et al. Murine models of anaemia of inflammation: extramedullary haematopoiesis represents a species specific difference to human anaemia of inflammation that can be eliminated by splenectomy. Int J Immunopathol Pharmacol. 2008;21:577–584
  11. Jurado RL. Iron, infections, and anemia of inflammation. Clin Infect Dis. 1997;25:888–895
  12. Poli-de-Figueiredo LF, Garrido AG, Nakagawa N, Sannomiya P. Experimental models of sepsis and their clinical relevance. Shock. 2008;30(Suppl 1):53–59
  13. Freise H, Bruckner UB, Spiegel HU. Animal models of sepsis. J Invest Surg. 2001;14:195–212
  14. Schubert T, Echtenacher B, Hofstadter F, Mannel DN. TNF-independent development of transient anemia of chronic disease in a mouse model of protracted septic peritonitis. Lab Invest. 2003;83:1743–1750
  15. Schubert TE, Echtenacher B, Hofstadter F, Mannel DN. Failure of interferon-gamma and tumor necrosis factor in mediating anemia of chronic disease in a mouse model of protracted septic peritonitis. Int J Mol Med. 2005;16:753–758
  16. Gallimore B, Gagnon RF, Subang R, Richards GK. Natural history of chronic Staphylococcus epidermidis foreign body infection in a mouse model. J Infect Dis. 1991;164:1220–1223
  17. Bunce C, Wheeler L, Reed G, Musser J, Barg N. Murine model of cutaneous infection with gram-positive cocci. Infect Immun. 1992;60:2636–2640
  18. Lee SW, Kang YA, Yoon YS, Um SW, Lee SM, Yoo CG, et al. The prevalence and evolution of anemia associated with tuberculosis. J Korean Med Sci. 2006;21:1028–1032
  19. Boelaert JR, Vandecasteele SJ, Appelberg R, Gordeuk VR. The effect of the host's iron status on tuberculosis. J Infect Dis. 2007;195:1745–1753
  20. Lounis N, Truffot-Pernot C, Grosset J, Gordeuk VR, Boelaert JR. Iron and Mycobacterium tuberculosis infection. J Clin Virol. 2001;20:123–126
  21. Marquis JF, Lacourse R, Ryan L, North RJ, Gros P. Genetic and functional characterization of the mouse Trl3 locus in defense against tuberculosis. J Immunol. 2009;182:3757–3767
  22. Ihedioha JI, Ochiogu IS, Ihedioha TE. Co-administration of Na-EDTA and diminazene aceturate (DA) to mice infected with DA-resistant Trypanosoma brucei. J Comp Pathol. 2007;136:206–211
  23. Amole BO, Clarkson AB, Shear HL. Pathogenesis of anemia in Trypanosoma brucei-infected mice. Infect Immun. 1982;36:1060–1068
  24. Emeribe AO, Anosa VO. Haematology of experimental Trypanosoma brucei gambiense infection (II. Erythrocyte and leucocyte changes). Rev Elev Med Vet Pays Trop. 1991;44:53–57
  25. Stijlemans B, Vankrunkelsven A, Brys L, Magez S, De BP. Role of iron homeostasis in trypanosomiasis-associated anemia. Immunobiology. 2008;213:823–835
  26. de MQ Nadjm B, Reyburn H, Kemna EH, Amos B, Laarakkers CM, et al. Assessment of urinary concentrations of hepcidin provides novel insight into disturbances in iron homeostasis during malarial infection. J Infect Dis. 2009;199:253–262
  27. Howard CT, McKakpo US, Quakyi IA, Bosompem KM, Addison EA, Sun K, et al. Relationship of hepcidin with parasitemia and anemia among patients with uncomplicated Plasmodium falciparum malaria in Ghana. Am J Trop Med Hyg. 2007;77:623–626
  28. 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;110:1037–1044
  29. Pak M, Lopez MA, Gabayan V, Ganz T, Rivera S. Suppression of hepcidin during anemia requires erythropoietic activity. Blood. 2006;108:3730–3735
  30. Vokurka M, Krijt J, Sulc K, Necas E. Hepcidin mRNA levels in mouse liver respond to inhibition of erythropoiesis. Physiol Res. 2006;55:667–674
  31. Thawani N, Tam M, Stevenson MM. STAT6-mediated suppression of erythropoiesis in an experimental model of malarial anemia. Haematologica. 2009;94:195–204
  32. Lamb TJ, Langhorne J. The severity of malarial anaemia in Plasmodium chabaudi infections of BALB/c mice is determined independently of the number of circulating parasites. Malar J. 2008;7:68
  33. Nunes JK, Starnbach MN, Wirth DF. Secreted antibody is required for immunity to Plasmodium berghei. Infect Immun. 2009;77:414–418
  34. Vigario AM, Belnoue E, Gruner AC, Mauduit M, Kayibanda M, Deschemin JC, et al. Recombinant human IFN-alpha inhibits cerebral malaria and reduces parasite burden in mice. J Immunol. 2007;178:6416–6425
  35. Hargreaves J, Yoeli M, Nussenzweig RS. Immunological studies in rodent malaria (I: Protective immunity induced in mice by mild strains of Plasmodium berghei yoelii against a virulent and fatal line of this plasmodium). Ann Trop Med Parasitol. 1975;69:289–299
  36. Frazer DM, Wilkins SJ, Millard KN, McKie AT, Vulpe CD, Anderson GJ. Increased hepcidin expression and hypoferraemia associated with an acute phase response are not affected by inactivation of HFE. Br J Haematol. 2004;126:434–436
  37. Mikolajew M, Stachurska J, Kalczak M, Lewicka S, Kossakowska M. [Hematologic changes in rats with adjuvant-induced disease. Intravascular clotting and fibrinolysis as a possible factor in the pathogenesis of anemia]. Reumatologia. 1975;13:47–56
  38. Wang Q, Liao QK. [Effect of nitric oxide on iron metabolism in rats with anemia of chronic disease]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2003;11:385–389
  39. Asai F, Oshima T. Recombinant human erythropoietin, but not iron supplementation, improves anemia in rats with adjuvant-induced arthritis. Jpn J Pharmacol. 1991;57:291–298
  40. Feldman BF, Kaneko JJ, Farver TB. Anemia of inflammatory disease in the dog: ferrokinetics of adjuvant-induced anemia. Am J Vet Res. 1981;42:583–585
  41. Sasu B, Hainu M, Boone TC, Bi X-J, Lee KJ, Arvedson T, et al. Hepcidin, hepcidin antagonists and methods of use. US Patent and Trade Office Application no. 20080213277; filed January 30, 2008.
  42. Kemna EH, Kartikasari AE, van Tits LJ, Pickkers P, Tjalsma H, Swinkels DW. Regulation of hepcidin: insights from biochemical analyses on human serum samples. Blood Cells Mol Dis. 2008;40:339–346
  43. Montosi G, Corradini E, Garuti C, Barelli S, Recalcati S, Cairo G, et al. Kupffer cells and macrophages are not required for hepatic hepcidin activation during iron overload. Hepatology. 2005;41:545–552
  44. Lasocki S, Millot S, Andrieu V, Letteron 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;36:2388–2394
  45. Sun XF, Zhou DB, Zhao YQ. [An iron regulator hepcidin is affected by EPO]. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2006;14:778–782
  46. Nemeth E, Rivera S, Gabayan V, Keller C, Taudorf S, Pedersen BK, et al. IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest. 2004;113:1271–1276
  47. Raja KB, Duane P, Peters TJ. Effects of turpentine-induced inflammation on the hypoxic stimulation of intestinal Fe3+ absorption in mice. Int J Exp Pathol. 1990;71:785–789
  48. Williams RO. Collagen-induced arthritis as a model for rheumatoid arthritis. Methods Mol Med. 2004;98:207–216
  49. Nemeth E, Valore EV, Territo M, Schiller G, Lichtenstein A, Ganz T. Hepcidin, a putative mediator of anemia of inflammation, is a type II acute-phase protein. Blood. 2003;101:2461–2463
  50. 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;306:2090–2093
  51. Katsume A, Saito H, Yamada Y, Yorozu K, Ueda O, Akamatsu K, et al. Anti-interleukin 6 (IL-6) receptor antibody suppresses Castleman's disease like symptoms emerged in IL-6 transgenic mice. Cytokine. 2002;20:304–311
  52. Sartor RB, Anderle SK, Rifai N, Goo DA, Cromartie WJ, Schwab JH. Protracted anemia associated with chronic, relapsing systemic inflammation induced by arthropathic peptidoglycan-polysaccharide polymers in rats. Infect Immun. 1989;57:1177–1185
  53. 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;113:5277–5286
  54. Coccia MA, Cooke K, Stoney G, Pistillo J, Del CJ, Duryea D, et al. Novel erythropoiesis stimulating protein (darbepoetin alfa) alleviates anemia associated with chronic inflammatory disease in a rodent model. Exp Hematol. 2001;29:1201–1209
  55. Foller M, Biswas R, Mahmud H, Akel A, Shumilina E, Wieder T, et al. Effect of peptidoglycans on erythrocyte survival. Int J Med Microbiol. 2009;299:75–85
  56. Uchiyama Y, Koike N, Mihara M. Anemia in monkey collagen-induced arthritis is correlated with serum IL-6, but not TNFalpha. Rheumatol Int. 2008;28:879–883
  57. Hu X, Camus AC, Aono S, Morrison EE, Dennis J, Nusbaum KE, et al. Channel catfish hepcidin expression in infection and anemia. Comp Immunol Microbiol Infect Dis. 2007;30:55–69
  58. Shike H, Lauth X, Westerman ME, Ostland VE, Carlberg JM, Van Olst JC, et al. Bass hepcidin is a novel antimicrobial peptide induced by bacterial challenge. Eur J Biochem. 2002;269:2232–2237
  59. Shike H, Shimizu C, Lauth X, Burns JC. Organization and expression analysis of the zebrafish hepcidin gene, an antimicrobial peptide gene conserved among vertebrates. Dev Comp Immunol. 2004;28:747–754

 The work described in this report was funded in part by NIH NIDDK/NHLBI 1K08DK074284-01.

PII: S0037-1963(09)00100-0

doi: 10.1053/j.seminhematol.2009.06.003

Seminars in Hematology
Volume 46, Issue 4 , Pages 351-357 , October 2009

Article Tools

* Image Usage & Resolution