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Effects of chloroquine treatment on circulating erythropoietin and inflammatory cytokines in acute Plasmodium falciparum malaria

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Abstract

Anemia is a common and serious complication of malaria due to Plasmodium falciparum infection, a major health problem in tropical areas. Herein, the relation was investigated between the levels of circulating erythropoietin (EPO) and immunomodulatory cytokines in response to chloroquine treatment. Thirty-seven healthy control subjects and 40 patients with acute P. falciparum infection were included in the study. All subjects were adult male Sudanese. Blood samples were collected before chloroquine administration (25 mg/kg body weight, orally on three consecutive days) and 3 and 30 days after start of the therapy. Measurements included routine hematological parameters and the concentrations of immunoreactive EPO, tumor necrosis factor-α (TNF-α), interleukin 1α (IL-1), IL-6, and interferon γ (INF-γ). Chloroquine treatment led to a decrease in EPO levels in the control subjects but an increase in malaria patients at day 30. The latter was likely due to the anti-inflammatory action of the drug because INF-γ, IL-1, and IL-6 concentrations declined on chloroquine treatment. Based on these findings, we propose that an impaired EPO production in association with a prolonged elevation of certain inflammatory cytokines can contribute to the anemia in some malaria patients which can be reversed by chloroquine therapy.

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References

  1. Brown AE, Webster HK, Teja IP, Keeratithakul D (1990) Macrophage activation in falciparum malaria as measured by neopterin and interferon-gamma. Clin Exp Immunol 82:97–101

    Article  PubMed  CAS  Google Scholar 

  2. Burchard GD, Radloff P, Philipps J, Nkeyi M, Knobloch J, Kremsner PG (1995) Increased erythropoietin production in children with severe malarial anemia. Am J Trop Med Hyg 53:547–551

    PubMed  CAS  Google Scholar 

  3. Burgmann H, Looareesuwan S, Kapiotis S, Viravan C, Vanijanonta S, Hollenstein U et al (1996) Serum levels of erythropoietin in acute Plasmodium falciparum malaria. Am J Trop Med Hyg 54:280–283

    PubMed  CAS  Google Scholar 

  4. Chang KH, Stevenson MM (2004) Effect of anemia and renal cytokine production on erythropoietin production during blood-stage malaria. Kidney Int 65:1640–1646 . doi:10.1111/j.1523-1755.2004.00573.x

    Article  PubMed  CAS  Google Scholar 

  5. Elamin SB, Malik EM, Abdelgadir T, Khamiss AH, Mohammed MM, Ahmed ES et al (2005) Artesunate plus sulfadoxine-pyrimethamine for treatment of uncomplicated Plasmodium falciparum malaria in Sudan. Malar J 4:41 . doi:10.1186/1475-2875-4-41

    Article  PubMed  CAS  Google Scholar 

  6. el-Hassan AM, Saeed AM, Fandrey J, Jelkmann W (1997) Decreased erythropoietin response in Plasmodium falciparum malaria-associated anaemia. Eur J Haematol 59:299–304

    Article  PubMed  CAS  Google Scholar 

  7. Fievet N, Moussa M, Tami G, Maubert B, Cot M, Deloron P et al (2001) Plasmodium falciparum induces a Th1/Th2 disequilibrium, favoring the Th1-type pathway, in the human placenta. J Infect Dis 183:1530–1534 . doi:10.1086/320201

    Article  PubMed  CAS  Google Scholar 

  8. Frisk-Holmberg M, Bergkvist Y, Domeij-Nyberg B, Hellstrom L, Jansson F (1979) Chloroquine serum concentration and side effects: evidence for dose-dependent kinetics. Clin Pharmacol Ther 25:345–350

    PubMed  CAS  Google Scholar 

  9. Hemmer CJ, Kern P, Holst FG, Radtke KP, Egbring R, Bierhaus A et al (1991) Activation of the host response in human Plasmodium falciparum malaria: relation of parasitemia to tumor necrosis factor/cachectin, thrombin-antithrombin III, and protein C levels. Am J Med 91:37–44 . doi:10.1016/0002-9343(91)90071-5

    Article  PubMed  CAS  Google Scholar 

  10. Jelkmann W (1998) Proinflammatory cytokines lowering erythropoietin production. J Interferon Cytokine Res 18:555–559

    Article  PubMed  CAS  Google Scholar 

  11. Kurtzhals JA, Rodrigues O, Addae M, Commey JO, Nkrumah FK, Hviid L (1997) Reversible suppression of bone marrow response to erythropoietin in Plasmodium falciparum malaria. Br J Haematol 97:169–174 . doi:10.1046/j.1365-2141.1997.82654.x

    Article  PubMed  CAS  Google Scholar 

  12. Lamikanra AA, Brown DM, Potocnik A, Casals-Pascual C, Langhorne J, Roberts DJ (2007) Malarial anemia: of mice and man. Blood 110:18–28 . doi:10.1182/blood-2006-09-018069

    Article  PubMed  CAS  Google Scholar 

  13. Malik EM, Mohamed TA, Elmardi KA, Mowien RM, Elhassan AH, Elamin SB et al (2006) From chloroquine to artemisinin-based combination therapy: the Sudanese experience. Malar J 5:65 . doi:10.1186/1475-2875-5-65

    Article  PubMed  CAS  Google Scholar 

  14. McDevitt MA, Xie J, Gordeuk V, Bucala R (2004) The anemia of malaria infection: role of inflammatory cytokines. Curr Hematol Rep 3:97–106

    PubMed  Google Scholar 

  15. Means RT, Krantz SB (1992) Progress in understanding the pathogenesis of the anemia of chronic disease. Blood 80:1639–1647

    PubMed  Google Scholar 

  16. Nussenblatt V, Mukasa G, Metzger A, Ndeezi G, Garrett E, Semba RD (2001) Anemia and interleukin-10, tumor necrosis factor alpha, and erythropoietin levels among children with acute, uncomplicated plasmodium falciparum malaria. Clin Diagn Lab Immunol 8:1164–1170 . doi:10.1128/CDLI.8.6.1164-1170.2001

    Article  PubMed  CAS  Google Scholar 

  17. Tagelsir N, Ibrahim Z, Medani A, Salih O, Hamad A, Giha H et al (2006) High frequency of Plasmodium falciparum PfCRT K76T and PfpghN86Y in patients clearing infection after chloroquine treatment in the Sudan. Acta Trop 97:19–25 . doi:10.1016/j.actatropica.2005.07.030

    Article  PubMed  CAS  Google Scholar 

  18. Verhoef H, West CE, Kraaijenhagen R, Nzyuko SM, King R, Mbandi MM et al (2002) Malarial anemia leads to adequately increased erythropoiesis in asymptomatic Kenyan children. Blood 100:3489–3494 . doi:10.1182/blood-2001-12-0228

    Article  PubMed  CAS  Google Scholar 

  19. Weatherall DJ, Abdalla S (1982) The anaemia of Plasmodium falciparum malaria. Br Med Bull 38:147–151

    PubMed  CAS  Google Scholar 

  20. Weiss G, Goodnough LT (2005) Anemia of chronic disease. N Engl J Med 352:1011–1023 . doi:10.1056/NEJMra041809

    Article  PubMed  CAS  Google Scholar 

  21. Wenisch C, Parschalk B, Narzt E, Looareesuwan S, Graninger W (1995) Elevated serum levels of IL-10 and IFN-gamma in patients with acute Plasmodium falciparum malaria. Clin Immunol Immunopathol 74:115–117 . doi:10.1006/clin.1995.1017

    Article  PubMed  CAS  Google Scholar 

  22. Word Health Organisation (1968) Nutritional anaemias. Report of a WHO scientific group.405:5–37

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Acknowledgment

Supported by DAAD, grant No. A/99/04652.

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Correspondence to Wolfgang Jelkmann.

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Ballal, A., Saeed, A., Rouina, P. et al. Effects of chloroquine treatment on circulating erythropoietin and inflammatory cytokines in acute Plasmodium falciparum malaria. Ann Hematol 88, 411–415 (2009). https://doi.org/10.1007/s00277-008-0636-z

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  • DOI: https://doi.org/10.1007/s00277-008-0636-z

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