Skip to main content
SpringerLink
Log in

Interaction of inflammatory cytokines and erythropoeitin in iron metabolism and erythropoiesis in anaemia of chronic disease

  • Published:
Clinical Rheumatology Aims and scope Submit manuscript

Summary

In chronic inflammatory conditions increased endogenous release of specific cytokines (TNFα, IL-1, IL-6, IFNγ and others) is presumed. It has been shown that those of monocyte lineage play a key role in cytokine expression and synthesis. This may be associated with changes in iron metabolism and impaired erythropoiesis and may lead to development of anaemia in patients with rheumatoid arthritis.

Firstly, increased synthesis of acute phase proteins, like ferritin, during chronic inflammation is proposed as the way by which the toxic effect of iron and thereby the synthesis of free oxy-radicals causing the damage on the affected joints, may be reduced. This is associated with a shift of iron towards the mononuclear phagocyte system which may participate in the development of anaemia of chronic disease.

Secondly, an inhibitory action of inflammatory cytokines (TNFα, IL-1), on proliferation and differentiation of erythroid progenitors as well as on synthesis of erythropoietin has been shown, thereby also contributing to anaemia.

Finally, chronic inflammation causes multiple, complex disturbances in the delicate physiologic equilibrium of interaction between cytokines and cells (erythroid progenitors, cells of mononuclear phagocyte system and erythropoietin producing cells) leading to development of anaemia of chronic disease (Fig. 1).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hansen, N.E. The anaemia of chronic disorders: A bag of unsolved questions. Scand J Haematol 1983, 31, 397–402.

    Google Scholar 

  2. Lee, G.R. The anaemia of chronic disease. Semin Hematol 1983, 20, 61–66.

    Google Scholar 

  3. Cartwright, G.E., Lee, G.R. The anemia of chronic disorders. Br J Haematol 1979, 39, 437–444.

    Google Scholar 

  4. Vreugdenhil, G., Wognum, A.W., Van Eijk, H.G., Swaak, A.J.G. Anemia in rheumatoid arthritis. The role of iron, vitamin B12 and folic acid deficiency and erythropoietin responsiveness. Ann Rheum Dis 1990, 49, 93–98.

    Google Scholar 

  5. Mowat, A.G. Hematologic abnormalities in rheumatoid arthritis. Semin Arthritis Rheum 1971, 1, 383–390.

    Google Scholar 

  6. Vreugdenhil, G., Swaak, A.J.G. Anaemia in theumatoid arthritis: pathogenesis, diagnosis and treatment. Rheumatol Int 1990, 9, 243–257.

    Google Scholar 

  7. Fillet, G., Beguin, Y., Baldelli, L. Model of reticuloendothelial iron metabolism in humans: Abnormal behavior in idiopathic haemochromatosis and inflammation. Blood 1989, 74, 844–851.

    Google Scholar 

  8. Roester, H.P. Iron metabolism in inflammation and malignant disease. In: Iron in Biochemistry and Medicine II, Eds.: Jacobs, A. Worwood, M., London, Academic Press, 1980, 605–640.

    Google Scholar 

  9. Raja, K.B., Simpson, R.J., Pippard, M.J., Peters, T.J. In vivo studies of the relationship between intestinal iron (Fe3+) absorption, hypoxia and erythropoiesis. Br J Haematol 1988, 68, 373–378.

    Google Scholar 

  10. Conrad, M.E., Barton, J.C. Factors affecting iron balance. Am J Hematol 1981, 10, 199–225.

    Google Scholar 

  11. Torti, S.V., Kwaak, E.L., Miller, S.C., Miller, L.L., Ringold, G.M., Myambo, K.B., Young, A.P., Torti, F.M. The molecular cloning and characterization of murine ferritin heavy chain, a tumor necrosis factor-inducible gene. J Biol Chem 1988, 263, 12638–12644.

    Google Scholar 

  12. Alvarez-Hernandez, X., Liceaga, J., McKay, I.C., Brock, J.H. Induction of hypoferremia and modulation of macrophage iron metabolism by tumor necrosis factor. Lab Invest 1989, 61, 319–322.

    Google Scholar 

  13. Roger, J., Durmowicz, G., Kasschau, K., Lacroix, L., Bridges, K. A motif within the 5'non-coding regions of acute phase mRNA mediates ferritin translation by interleukin-1beta and may contribute to the anemia of chronic disease. Blood 1991, 78, 367a.

    Google Scholar 

  14. Fuchs, J., Hausen, A., Reibnegger, G., Werner, E., Werner-Felmayer, G., Dierich, M., Wacher, H. Immune activation and the anemia associated with chronic inflammatory disorders. Eur J Haematol 1991, 46, 65–70.

    Google Scholar 

  15. Qusenberry, P. Stromal regulation of haematopoiesis. In: Molecular and Cellular Control of Hematopoiesis, Ed.: Orlic, D.H., New York, The New York Academy of Science, 1989, 116.

    Google Scholar 

  16. Bondurant, M.C., Koury, M.J. Anemia induces accumulation of erythropoietin mRNA in the kidney and liver. Mol Cell Biol 1986, 6, 2731–2733.

    Google Scholar 

  17. Koury, M.J., Bondurant, M.C., Graber, S.J., Sawyer, S.T. Erythropoietin gene expression in the kidney tissue detected by in situ hybridisation. Blood 1982, 71, 524–527.

    Google Scholar 

  18. Rich, I.N., Heit, W., Kubanec, B. Extrarenal erythropoietin production by macrophages. Blood 1982, 60, 1007–1018.

    Google Scholar 

  19. Spivak, J.S. The mechanism of action of erythropoietin. Int J Cell Cloning 1986, 4, 139–166.

    Google Scholar 

  20. Baer, A.N., Dessypries, E.N., Goldwasser, E., Krantz, S.B. Blunted erythropoietin response to anaemia in rheumatoid arthritis. Br J Haematol 1987, 66, 559–564.

    Google Scholar 

  21. Hochberg, M.C., Arnold, C.M., Hogans, B.B., Spivak, J.L. Serum immunoreactive erythropoietin in rheumatoid arthritis: impaired response to anemia. Arthritis Rheum 1988, 31, 1318–1321.

    Google Scholar 

  22. Boyd, H.K., Lappin, T.R.J., Bell, A.L. Evidence for impaired erythropoietin response to anemia in rheumatoid disease. Br J Rheumatol 1991, 30, 225–259.

    Google Scholar 

  23. Vreugdenhil, G., Kontoghiorghes, G.J., Van Eijk, H.G., Swaak, A.J.G. Impaired erythropoietin responsiveness to the anemia in rheumatoid arthritis. A possible inverse relationship with iron stores and effects of the oral chelator 1,2-dimethyl-3-hydroxypyrid-4-one. Clin Exp Rheumatol 1991, 9, 35–40.

    Google Scholar 

  24. Means, R.T., Olsen, N.J., Krantz, S.T., Dessypris, E.N., Graber, S.E., Stone, W.J., O'Neil, V.L., Pincus, T. Treatment of the anemia of rheumatoid arthritis with recombinant erythropoietin: clinical and in vivo studies. Arthritis Rheum 1989, 32, 638–642.

    Google Scholar 

  25. Pincus, T., Olsen, N.J., Russel, J., Wolfe, F., Harris, E.R., Boccagno, J.A., Krantz, S.B. Multicenter study of recombinant human erythropoietin in correction of anemia in rheumatoid arthritis. Am J Med 1990, 89, 161–168.

    Google Scholar 

  26. Vreugdenhil, G., Manger, B., Nieuwenhuizen, C., Feelders, R.A., Van Eijk, H.G., Swaak, A.J.G. Iron stores and serum transferrin receptor levels during recombinant human erythropoietin treatment of anemia in rheumatoid arthritis. Am J Hematol 1992, 65, 265–268.

    Google Scholar 

  27. Panay, G.S. The immunopathogenesis of rheumatoid arthritis. Br J Rheumatol 1993, 32 (suppl 1), 4–14.

    Google Scholar 

  28. Means, R.T., Krantz, S.B. Progress in understanding the pathogenesis of anemia of chronic disease. Blood 1992, 7, 1639–1647.

    Google Scholar 

  29. Roodman, G.D., Bird, A., Hutzer, D., Montgomery, W. Tumor necrosis factor-alpha and haematopoietic progenitors CFU-E and BFU-E and the haematopoietic cell lines K562, HL60 and HEL cells. Exp Hematol 1987, 15, 928–935.

    Google Scholar 

  30. Konjin, A.M., Camel, N., Levy, R., Hershko, C. Mechanism of ferritin synthesis in inflammation. Br J Haematol 1981, 49, 361–366.

    Google Scholar 

  31. Moldawer, L.L., Marano, M.A., Wei, H., Fong, Y., Silen, M.L., Kuo, G., Monague, K.R., Vlassara, H., Cohen, H., Cerami, A., Lowry, S. Cachectin/tumor necrosis factor-alpha alters red blood cell kinetics and induces anemia in vivo. FASEB J 1989, 3, 1637–1643.

    Google Scholar 

  32. Johnson, R.A., Waddelow, T.A., Caro, J., Oliff, A., Roodman, G.D. Chronic exposure to tumor necrosis factor in vivo preferentially inhibits erythropoiesis in nude mice. Blood 1989, 74, 130–138.

    Google Scholar 

  33. Fuchs, D., Hausen, A., Reibnegger, G., Werner, E.R., Werner-Felmayer, G., Dierich, M.P., Wachter, H. Immune activation and the anemia associated with chronic inflammatory disorders. Eur J Haematol 1991, 46, 65–70.

    Google Scholar 

  34. Murray, H.W. Interferon-gama, the activated macrophage, and host defence against microbial challenge. Ann Intern Med 1988, 108, 595–608.

    Google Scholar 

  35. Ozmen, L., Fountoulakis, M., Gentz, R., Garotta, G. Immunomodulation with soluble IFN-gamma receptor. Int Rev Exp Pathol 1993, 34, 137–147.

    Google Scholar 

  36. Denz, H., Fuchs, D., Huber, H., Nachtbaur, D., Reibnegger, G., Thaler, J., Werner, E.R., Wachter, H. Correlation between neopterin, interferon-gamma and haemoglobin in patients with hematological disorders. Eur J Haematol 1990, 44, 186–189.

    Google Scholar 

  37. Fuchs, D., Haussen, A., Reibnegger, G., Werner, E.R., Dierich, M.P., Wachter, H. Neopterin as a marker for activated cell-mediated immunity: Application in HIV infection. Immunol Today 1988, 9, 150–155.

    Google Scholar 

  38. Reibnegger, G., Egg, D., Fuchs, D. Urinary neopterin reflects clinical activity in patients with rheumatoid arthritis. Arthritis Rheum 1986, 29, 1063–1070.

    Google Scholar 

  39. Klausner, R.D., Harford, J.B. Cis-trans models for post-transcriptional gene regulation. Science 1989, 246, 870–872.

    Google Scholar 

  40. Skikne, B.S., Cook, J.D. Effect of enhanced erythropoiesis on iron absorption. J Lab Med 1992, 120, 746–751.

    Google Scholar 

  41. Cavill, I., Worwood, M., Jacobs, A. Internal regulation of iron absorption. Nature 1975, 256, 328–329.

    Google Scholar 

  42. Fey, G., Gauldine, J. The acute phase response of the liver in inflammation. In: Progress in Liver Disease, Eds.: Popper, H. Schaffner, F., Philadelphia, Saunders, W.B. Co., 1990, 89–116.

    Google Scholar 

  43. Baumann, H., Gauldie, J. Regulation of hepatic acute phase plasma protein genes by hepatocyte stimulation factors and other mediators of inflammation. Mol Biol Med 1990, 7, 147–159.

    Google Scholar 

  44. Baumann, H., Morella, K.K., Wong, G.H.W. TNF-alpha, IL-1beta and hepatocyte growth factor cooperate in stimulating specific acute phase plasma protein genes in rat hepatoma cells. J Immunol 1993, 151, 4248–4257.

    Google Scholar 

  45. Invernizzi, R., Cazzola, M., De Fazio, P., Cooper, S., Leve, S., Salfeld, J., Arosio, P. Immunocytochemical detection of ferritin in human bone marrow and peripheral blood cells using monoclonal antibodies specific for the H and L subunits. Br J Haematol 1990, 76, 427–432.

    Google Scholar 

  46. Broxmeyer, H., Bicknell, D.C., Williams, D.E., Cooper, S., Leve, S., Salfeld, J., Arosio, P. The influence of purified recombinant human heavy-subunit and light-subunit ferritin on colony formation in vitro by granulocyte-macrophage and erythroid progenitor cells. Blood 1986, 68, 1257–1263.

    Google Scholar 

  47. Kushner, I. The phenomenon of acute phase response. Ann NY Acd Sci 1982, 386, 39–48.

    Google Scholar 

  48. Vreugdenhil, G., Koos, M.J., Van Eijk, H.G., Swaak, A.J.G. Impaired iron uptake and transferrin binding by erythroblast in the anemia of rheumatoid arthritis. Br J Rheumatol 1990, 29, 335–339.

    Google Scholar 

  49. Feelders, R.A., Vreugdenhil, G., Van Dijk, J.P., Swaak, A.J.G., Van Eijk, H.G. Decreased affinity and number of transferrin receptors on erythroblasts in the anemia of rheumatic disease. Am J Hematol 1993, 43, 200–204.

    Google Scholar 

  50. Ferguson, B.J., Skikne, B.S., Simpson, K.M., Baynes, R.D., Cook, J.D. Serum transferrin receptor distinguishes the anaemia of chronic disease from iron deficiency anaemia. J Lab Clin Med 1992, 19, 385–390.

    Google Scholar 

  51. Pettersson, T., Kivivuori, S.M., Siimes, M.A. Is serum transferrin receptor useful for detecting iron-deficiency in anaemic patients with chronic inflammatory diseases? Br J Rheumatol 1994, 33, 740–744.

    Google Scholar 

  52. Zoli, A., Altomonte, L., Mirone, L., Magaro, M., Ricerca, B.M., Storti, S., Candido, A., Bizzi, M. Serum transferrin receptors in rheumatoid arthritis. Ann Rheum Dis 1994, 53, 699–701.

    Google Scholar 

  53. Graziadei, I., Braunsteiner, H., Vogel, W. The hepatic acute-phase proteins alpha-1-antitripsin and alpha-2-macroglobulin inhibit binding of transferrin to its receptor. Biochem J 1993, 290, 109–113.

    Google Scholar 

  54. Graziadei, I., Gaggl, S., Kasesrbacher, R., Braunsteiner, H., Vogel, W. The acute-phase protein alpha-1-antitripsin inhibits growth and proliferation of human early erythroid progenitor cells (burstforming unit-erythroid) and human erythroleukemic cells (K562) in vitro by interfering with transferrin iron uptake. Blood 1994, 83, 260–268.

    Google Scholar 

  55. Mackiewicz, A., Kusher, I. Transforming growth factor beta-1 influences glycosylation of alpha-1-protease inhibitor in human hepatoma cell lines. Inflammation 1990, 5, 485–497.

    Google Scholar 

  56. Ramadori, G., Van Damme, J., Rieder, H., Meyer zum Buschenfelde, K. H. Interleukin 6, the third mediator of acute-phase reaction, modulates hepatic protein synthesis in human and mouse. Comparison with interleukin 1beta and tumor necrosis factor alpha. Eur J Immunol 1988, 18, 1259–1264.

    Google Scholar 

  57. Van Eijk, H.G., Van Noort, W.L., De Jong, G., Kooster, J.F. Human serum sialotransferrin in disease. Clin Chem Acta 1987, 165, 141–145.

    Google Scholar 

  58. Feelders, R.A., Vreugdenhil, G., De Jong, G., Swaak, A.J.G., Van Eijk, H.G. Transferrin microheterogenity in rheumatoid arthritis: Relating with disease activity and anemia of chronic disease. Rheumatol Int 1992, 12, 373–377.

    Google Scholar 

  59. Bortner, C.A., Miller, R.D., Arnold, R.R. Bactericidal effect of lactoferrin on Legionella pneumophila. Infect Immunol 1986, 51, 373–377.

    Google Scholar 

  60. Cash, J.A., Coates, T.D., Lafuze, J., Baehner, R.L., Boxer, L.A. Plasma lactoferrin reflects granulocyte activation in vivo. Blood 1983, 61, 885–888.

    Google Scholar 

  61. Bagby, G.C., McCall, E., Layman, D.L. Regulation of colony-stimulating activity production: Interaction of fibroblasts, mononuclear phagocytes and lactoferrin. J Clin Invest 1983, 71, 340–344.

    Google Scholar 

  62. Duncan, R.L., McArthur, W.P. Lactoferrin mediated modulation of mononuclear cell activities:suppression of murine in vitro primary antibody response. Cell Immunol 1981, 63, 308–320.

    Google Scholar 

  63. Nishiya, K., Horwitz, P.A. Contrasting effect of lactoferrin on human lymphocyte and monocyte natural killer cell activity and antibody-dependent cell-mediated cytotoxicity. J Immunol 1982, 129, 2519–2523.

    Google Scholar 

  64. Crouch, S.P.M., Slater, K.J., Fletcher, J. Regulation of cytokine release from mononuclear cells by the iron-binding protein lactoferrin. Blood 1992, 80, 235–240.

    Google Scholar 

  65. Djeha, A., Brock, J.H. Effect of transferrin, lactoferrin and chelated iron on human T-lymphocytes. Br J Haematol 1992, 80, 235–241.

    Google Scholar 

  66. Houston, T., Moore, M., Porter, D., Sturrock, R., Fitzsimons, E. Abnormal haem biosynthesis in the chronic anaemia of rheumatoid arthritis. Ann Rheum Dis 1994, 53, 167–170.

    Google Scholar 

  67. Pettersson, T., Rosenlöf, K., Laitinen, E., Tenhunen, R. Effect of exogenous erythropoietin on haem synthesis in anaemic patients with rheumatoid arthritis. Br J Rheumatol 1994, 33, 526–529.

    Google Scholar 

  68. Sugimoto, M., Wakabayschi, Y., Hirose, S. Immunological aspects of the anemia of rheumatoid arthritis. Am J Hematol 1987, 25, 1–11.

    Google Scholar 

  69. Reid, C.D.L., Prouse, P.J., Baptista, L.C. The mechanism of the anemia of rheumatoid arthritis: effects of bone marrow adherent cells and of serum on in vitro erythropoiesis. Br J Haematol 1984, 58, 607–615.

    Google Scholar 

  70. Harvey, A.R., Clarke, B.J., Chui, D.H.K. Anemia associated with rheumatoid disease. Inverse correlation between erythropoiesis and both IgM and rheumatoid factor levels. Arthritis Rheum 1983, 26, 28–34.

    Google Scholar 

  71. Gordon, L.I., Miller, W.J., Branda, R.F., Zanjani, E.D., Jacob, H.S. Regulation of erythroid formation by bone marrow macrophages. Blood 1988, 55, 1047–1050.

    Google Scholar 

  72. Akahane, K., Hosoi, T., Urabe, A., Kawakami, M., Takaku, F. Effects of recombinant human tumor necrosis factor (rhTNF) on normal human and mouse haematopoietic progenitor cells. Int J Cell Cloning 1987, 5, 16–26.

    Google Scholar 

  73. Backx, B., Broeders, L., Bot, F.J., Lowenberg, B. Positive and negative effects of tumor necrosis factor on colony growth from highly purified normal marrow progenitors. Leukemia 1991, 5, 66–70.

    Google Scholar 

  74. Broxmeyer, H.E., Williams, D.E., Lu, L., Cooper, S., Anderson, S.L., Beyer, G.S., Hoffman, R., Rubin, B.Y. The suppressive effect of human tumor necrosis factor on bone marrow haematopoietic progenitor cells from normal donors and patients with leukaemia: synergism of tumor necrosis factor and interferon-gamma. J Immunol 1986, 136, 4487–4495.

    Google Scholar 

  75. Means, R.T.Jr., Dessypris, E.N., Krantz, S.B. Inhibition of human colony-forming-unit erythroid by tumor necrosis factor requires accessory cells. J Clin Invest 1990, 86, 538–541.

    Google Scholar 

  76. Means, R.T.Jr., Krantz, S.B. Inhibition of human erythroid colony-forming units by tumor necrosis factor requires beta interferon. J Clin Invest 1993, 91, 416–419.

    Google Scholar 

  77. Means, R.T., Dessypris, E.N., Krantz, S.B. Inhibition of human erythroid colony-forming units by interleukin-1 is mediated by gamma interferon. J Cell Physiol 1992, 150, 59–64.

    Google Scholar 

  78. Vreugdenhil, G., Lowenberg, B., Van Eijk, H.G., Swaak, A.J.G. Tumor necrosis factor alpha is associated with disease activity and degree of anaemia in patients with rheumatoid arthritis. Eur J Clin Invest 1992, 22, 488–493.

    Google Scholar 

  79. Maury, C.J.P., Lahdevirta, J. Correlation of serum cytokine levels with haematological abnormalities in human immunodeficiency virus infection. J Int Med 1990, 227, 253–257.

    Google Scholar 

  80. Maury, C.J.P., Anderson, L.C., Teppo, A.M., Partanen, S., Juvonen, E. Mechanism of the anaemia in rheumatoid arthritis: Demonstration of raised interleukin 1beta concentrations in anaemic patients and of interleukin 1 mediated suppression of normal erythropoiesis and proliferation of human erythroleukemia (HEL). Ann Rheum Dis 1988, 47, 972–987.

    Google Scholar 

  81. Mamus, S.W., Beck-Schroeder, S., Zanjani, E.D. Suppression of normal human erythropoiesis by gamma interferon in vitro: Role of monocytes and T-lymphocytes. J Clin Invest 1985, 74, 1496–1503.

    Google Scholar 

  82. Raefsky, E.L., Platanias, L.C., Zoumbos, N.C., Young, N.S. Studies of interferon as a regulator of haematopoietic cell proliferation. J Immunol 1985, 135, 2507–2512.

    Google Scholar 

  83. Remacha, A.F., Rodrigues-de la Serna, A., Garcia-Die, F., Geli, C., Gimferrer, E. Erythroid abnormalities in rheumatoid arthritis: The role of erythropoietin. J Rheumatol 1992, 19, 1687–1691.

    Google Scholar 

  84. Erslev, A.J., Caro, J., Miller, O., Silver, R. Plasma erythropoietin in health and disease. Ann Clin Lab Sci 1980, 10, 24–27.

    Google Scholar 

  85. Jelkman, W., Pagel, H., Wolff, M., Fandrey, J. Monokines inhibiting erythropoietin production in human hepatoma cultures and in isolated perfused rat kidneys. Life Sci 1992, 50, 301–308.

    Google Scholar 

  86. Koury, M.J., Kelley, L.L., Bondurant, M.C. The fate of erythroid progenitor cells. Ann NY Acad Sci 1994, 718, 259–265.

    Google Scholar 

  87. Faquin, W.C., Schneider, T.J., Goldberg, M.A. Affect of inflammatory cytokines on hypoxia-induced erythropoietin production. Blood 1992, 79, 1987–1994.

    Google Scholar 

  88. Birgegaard, G., Gudbjornsson, B., Hallgren, R., Wilde, L. Anaemia of chronic inflammatory arthritides: treatment with recombinant human erythropoietin. Contrib Nephrol 1991, 88, 295–303.

    Google Scholar 

  89. Johnson, C.S., Cook, C.A., Furmanski, P., In vivo suppression of erythropoiesis by tumor necrosis factor-alpha (TNF-alpha): Reversal with exogenous erythropoietin (EPO). Exp Hematol 1990. 18, 109–113.

    Google Scholar 

  90. Jongen-Lavrencic, M., Peeters, H.R.M., Backx, B., Touw, I.P., Vreugdenhil, G., Swaak, A.J.G. r-h-Erythropoietin counteracts the inhibition of in vitro erythropoiesis by tumour necrosis factor alpha in patients with rheumatoid arthritis. Rheumatol Int 1994, 14, 109–113.

    Google Scholar 

  91. Jongen-Lavrencic, M., Peeters, H.R.M., Wognum, A.W., Vreugdenhil, G., Swaak, A.J.G. Erythropoietin receptor expression on bone marrow cells from rheumatoid arthritis patients with anaemia of chronic disease and control patients. Clin Rheumatol 1994, 13, 176.

    Google Scholar 

  92. Rogers, J., Lacroix, L., Durmowitz, G., Kasschau, K., Andriotakis, J., Bridges, K. The role of cytokines in the regulation of ferritin expression. 11th International Conference on Iron and Iron Proteins, 1993, 37.

  93. Weis, G., Goossen, B., Doppler, W. Translational regulation via iron-responsive elements by the nitric oxide/NO synthase pathway. EMBO J 1993, 12, 3651–3657.

    Google Scholar 

  94. Konijn, A.M., Hershko, C. The anaemia of inflammation and chronic disease. In: Iron in Immunity, Cancer and Inflammation., Eds.: Sousa de, M., Brock, J.M., Chichester, John Wiley, 1989, 111–143.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Rheumatology, Dr. Daniel den Hoed Clinic, Postbus 5201, 3008 AE, Rotterdam, The Netherland

    M. Jongen-Lavrencic, H. R. M. Peeters & A. J. G. Swaak

  2. Department of Internal Medicine, St. Joseph Hospital Eindhoven, The Netherlands

    G. Vreugdenhil

Authors
  1. M. Jongen-Lavrencic
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. H. R. M. Peeters
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. Vreugdenhil
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. J. G. Swaak
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jongen-Lavrencic, M., Peeters, H.R.M., Vreugdenhil, G. et al. Interaction of inflammatory cytokines and erythropoeitin in iron metabolism and erythropoiesis in anaemia of chronic disease. Clin Rheumatol 14, 519–525 (1995). https://doi.org/10.1007/BF02208148

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02208148

Key words

Search

Navigation