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Interleukin-1 and Tumor Necrosis Factor-α Suppress Hypoxia-Induced Production of Erythropoietin In Vitro

  • M. Wolff
  • W. Jelkmann
  • J. Fandrey

Abstract

The glycoprotein growth factor erythropoietin (EPO) is primarily produced by the fetal liver and by the kidney in adults. EPO specifically stimulates the proliferation and maturation of erythroid precursor cells, especially colony and burst forming units-erythroid in the bone marrow [17]. Stimuli for EPO synthesis and secretion can be various kinds of lowered O2 supply to a still poorly defined sensor mechanism [2]. Human EPO serum levels increase in response to hypobaric hypoxia [9] or hypoxic hypoxia [14]. Acute hemorrhage in humans results in a transient elevation of EPO production [5, 28, 32]. In chronic anemia there is an inverse relationship between hemoglobin concentration and the serum EPO level [10, 18]. Thus, EPO production would be expected to be greatly stimulated following surgical or accidental blood loss or in septicemia with respiratory failure. However, EPO is inappropriately low for the degree of anemia in patients with chronic renal failure [25], inflammatory [4, 19] and malignant disease [29], or in acute renal allograft rejection [3]. A common feature among these anemia-associated conditions, that is shared with severe trauma, burning, and sepsis [11], is the release of cytokines by activated monocytes [1, 8, 15, 16, 24, 34]. These monokines, namely, interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), have been shown to evoke systemic reactions in critically ill patients known as acute-phase response [11].

Keywords

HepG2 Cell Hypobaric Hypoxia Erythropoietin Production Acute Hypobaric Hypoxia Human Hepatoma Cell Line HepG2 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Balkwill F, Osborne R, Burke F, Naylor S, Talbot D, Durbin H, Tavernier J, Fiers W (1987) Evidence for tumor necrosis factor/cachectin production in cancer. Lancet II:1229–1232CrossRefGoogle Scholar
  2. 2.
    Bauer C, Kurtz A (1989) Oxygen sensing in the kidney and its relation to erythropoietin production. Annu Rev Physiol 51:845–856PubMedCrossRefGoogle Scholar
  3. 3.
    Besarab A, Caro J, Jarrell BE, Francos G, Erslev AJ (1987) Dynamics of erythropoiesis following renal transplantation. Kidney Int 32:526–536PubMedCrossRefGoogle Scholar
  4. 4.
    Birgegard G (1989) Erythropoiesis and inflammation. Contrib Nephrol 76:330–341PubMedGoogle Scholar
  5. 5.
    Cotes PM (1989) Physiological studies of erythropoietin in plasma. In: Jelkmann W, Gross AJ (eds) Erythropoietin. Springer, Berlin Heidelberg New York, pp 57–79CrossRefGoogle Scholar
  6. 6.
    Darlington GJ, Wilson DR, Lachman LB (1986) Monocyte-conditioned medium, interleukin-1, and tumor necrosis factor stimulate the acute phase response in human hepatoma cells in vitro. J Cell Biol 103:787–793PubMedCrossRefGoogle Scholar
  7. 7.
    Dinarello CA (1987) The biology of interleukin 1 in comparison to tumor necrosis factor. Immunol Lett 16:227–232PubMedCrossRefGoogle Scholar
  8. 8.
    Eastgate JA, Symons JA, Wood NC, Grinlinton FM, Di Giovine FS, Duff GW (1988) Correlation of plasma interleukin-1 levels with disease activity in rheumatoid arthritis. Lancet II:706–709CrossRefGoogle Scholar
  9. 9.
    Eckhardt KU, Boutellier U, Kurtz A, Schopen M, Koller EA, Bauer C (1989) Rate of erythropoietin formation in humans in response to acute hypobaric hypoxia. J Appl Physiol 66:1785–1788Google Scholar
  10. 10.
    Erslev AJ, Wilson J, Caro J (1987) Erythropoietin titers in anemic, nonuremic patients. J Lab Clin Med 109:429–433PubMedGoogle Scholar
  11. 11.
    Faist E, Ninnemann J, Green D (eds) (1989) Immune consequences of trauma, shock, and sepsis. Mechanisms and therapeutical approaches. Springer, Berlin Heidelberg New YorkGoogle Scholar
  12. 12.
    Goldberg MA, Glass GA, Cunningham JM, Bunn HF (1987) The regulated expression of erythropoietin by two human hepatoma cell lines. Proc Natl Acad Sci USA 84:7972–7976PubMedCrossRefGoogle Scholar
  13. 13.
    Gould SA, Rosen AI, Sehgal LR, Sehgal HL, Rice CL, Chamberlin WH, Moss GS (1985) Depressed red cell recovery following acute blood loss. Fed Proc 44:1265Google Scholar
  14. 14.
    Haga P, Cotes PM, Till JA, Minty BD, Shinebourne EA (1987) Serum immunoreactive erythropoietin in children with cyanotic and acyanotic congenital heart disease. Blood 70:822–826PubMedGoogle Scholar
  15. 15.
    Herbelin A, Nguyen AT, Zingraff J, Urena P, Decamps-Latscha B (1990) Influence of uremia and hemodialysis on circulating interleukin-1 and tumor necrosis factor a. Kidney Int 37:116–125PubMedCrossRefGoogle Scholar
  16. 16.
    Imagawa DK, Millis JM, Olthoff KM, Derus LJ, Clna D, Sugich LR, Ozawa M, Dempsey RA, Iwaki Y, Levy PJ, Terasaki PI, Busuttil RW (1990) The role of tumor necrosis factor in allograft rejection. Transplantation 50:219–225PubMedCrossRefGoogle Scholar
  17. 17.
    Jelkmann W (1986) Renal erythropoietin: properties and production. Rev Physiol Biochem Pharmacol 104:139–215PubMedCrossRefGoogle Scholar
  18. 18.
    Jelkmann W, Wiedemann G (1990) Serum erythropoietin level: relationship to blood hemoglobin concentration and erythrocytic activity of the bone marrow. Klin Wochenschr 68:403–407PubMedCrossRefGoogle Scholar
  19. 19.
    Jelkmann W, Wolff M, Fandrey J (1990) Modulation of the production of erythropoietin by cytokines: in vitro studies and their clinical implications. Contrib Nephrol 87:68–77PubMedGoogle Scholar
  20. 20.
    Jensen MD (1976) Diffusion in tissue cultures on gas-permeable and gas-impermeable supports. J Theor Biol 56:443–458PubMedCrossRefGoogle Scholar
  21. 21.
    Johnson RA, Waddelow TA, Caro J, Oliff A, Roodman GD (1989) Chronic exposure to tumor necrosis factor in vivo preferentially inhibits erythropoiesis in nude mice. Blood 74:130–138PubMedGoogle Scholar
  22. 22.
    Le J, Vilcek J (1987) Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest 56:234–248PubMedGoogle Scholar
  23. 23.
    Levine EA, Gould SA, Rosen AL, Sehgal LR, Egrie JC, Sehgal HL, Revine HD, Moss GS (1989) Perioperative recombinant human erythropoietin. Surgery 106:432–438PubMedGoogle Scholar
  24. 24.
    Maury CPJ, Teppo AM (1988) Serum immunoreactive interleukin 1 in renal transplant recipients. Transplantation 45:143–147PubMedCrossRefGoogle Scholar
  25. 25.
    McGonigle RJS, Wallin JD, Shadduck RK, Fisher JW (1984) Erythropoietin deficiency and inhibition of erythropoiesis in renal insufficiency. Kidney Int 25:437–444PubMedCrossRefGoogle Scholar
  26. 26.
    McLimans WF, Blumenson LE, Tunnah KV (1968) Kinetics of gas diffusion in mammalian cell culture systems: II. Theory. Biotechnol Bioeng 10:741–763CrossRefGoogle Scholar
  27. 27.
    Means RT, Olsen NJ, Krantz SB, Dessypris EN, Graber SE, Stone WJ, O’Neil VL, Pincus T (1989) Treatment of the anemia of rheumatoid arthritis with recombinant human erythropoietin: clinical and in vitro studies. Arthritis Rheum 32:638–642PubMedCrossRefGoogle Scholar
  28. 28.
    Miller ME, Cronkite EP, Garcia JF (1982) Plasma levels of immunoreactive erythropoietin after acute blood loss in man. Br J Haematol 52:545–549PubMedCrossRefGoogle Scholar
  29. 29.
    Miller CB, Jones RJ, Piantadosi S, Abeloff MD, Spivak JL (1990) Decreased erythropoietin response in patients with the anemia of cancer. N Engl J Med 322:1689–1692PubMedCrossRefGoogle Scholar
  30. 30.
    Nielsen OJ, Schuster SJ, Kaufman R, Erslev AJ, Caro J (1987) Regulation of erythropoietin production in a human hepatoblastoma cell line. Blood 70:1904–1909PubMedGoogle Scholar
  31. 31.
    Perlmutter DH, Dinarello CA, Punsal PI, Colten HR (1986) Cachectin/tumor necrosis factor regulates hepatic acute-phase gene expression. J Clin Invest 78:1349–1354PubMedCrossRefGoogle Scholar
  32. 32.
    Rhyner K, Egli F, Niemöller M, Wieczorek A, Greminger P, Vetter W (1989) Serumerythropoie-tinwerte bei verschiedenen Krankheitszuständen. Nephron 51 (Suppl 1):39–46PubMedCrossRefGoogle Scholar
  33. 33.
    Roodman G (1987) Mechanisms of erythroid suppression in the anemia of chronic disease. Blood Cells 13:171–184PubMedGoogle Scholar
  34. 34.
    Saxne T, Palladino A, Heinegard D, Talal N, Wollheim A (1988) Detection of tumor necrosis factor a but not tumor necrosis factor ß in rheumatoid arthritis synovial fluid and serum. Arthritis Rheum 31:1041–1045PubMedCrossRefGoogle Scholar
  35. 35.
    Schooley JC, Kullgren B, Allison AC (1987) Inhibition by interleukin-1 of the action of erythropoietin on erythroid precursors and its possible role in the pathogenesis of hypoplastic anemias. Br J Haematol 67:11–17PubMedCrossRefGoogle Scholar
  36. 36.
    Tracey KJ, Wei H, Manogue KR, Fong Y, Hesse DG, Nguyen HT, Kuo GC, Beutler B, Cotran RS, Cerami A, Lowry SF (1988) Cachectin/tumor necrosis factor induces cachexia, anemia, and inflammation. J Exp Med 167:1211–1227PubMedCrossRefGoogle Scholar
  37. 37.
    Ueno M, Seferynska I, Beckman B, Brookins J, Nakashima J, Fisher JW (1989) Enhanced erythropoietin secretion in hepatoblastoma cells in response to hypoxia. Am J Physiol, 257:C743-C749PubMedGoogle Scholar
  38. 38.
    Ulich TR, del Castillo J, Guo KZ (1989) In vivo hematologic effects of recombinant interleukin-6 on hematopoiesis and circulating numbers of RBCs and WBCs. Blood 73:108PubMedGoogle Scholar
  39. 39.
    Wilson DF, Rumsey WL, Green TJ, Vanderkooi JM (1988) The oxygen dependence of mitochondrial oxidative phosphorylation measured by a new optical method for measuring oxygen concentration. J Biol Chem 263:2712–2718PubMedGoogle Scholar

Copyright information

© Springer-Verlag, Berlin Heidelberg 1993

Authors and Affiliations

  • M. Wolff
    • 1
  • W. Jelkmann
    • 1
  • J. Fandrey
    • 1
  1. 1.Physiologisches Institut IRheinische Friedrich-Wilhelms-Universität BonnBonnGermany

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