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

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


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].


HepG2 Cell Hypobaric Hypoxia Erythropoietin Production Acute Hypobaric Hypoxia Human Hepatoma Cell Line HepG2 
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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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