Monokines inhibiting erythropoietin production in human hepatoma cultures and in isolated perfused rat kidneys.
The blood level of erythropoietin (Epo) is often anomalously low in anemic patients with inflammatory or malignant diseases. Therefore, we studied effects of pure recombinant immunomodulatory peptides on Epo formation in cultures of the human hepatoma cell line, HepG2. Interleukin (IL)-1 beta, IL-1 alpha, and tumor necrosis factor alpha lowered Epo production with half-maximal inhibition at 2, 5, and 20 U/ml, respectively. IL-6, transforming growth factor beta 2 and interferon gamma did not inhibit. Furthermore, IL-1 beta (10 U/ml) proved to block Epo formation in isolated serum-free perfused rat kidneys. Proposedly, monokines play a role in the pathogenesis of Epo deficiency in various diseases.
Jelkmann
W
W
Department of Physiology, University of Bonn, Germany.
Pagel
H
H
Wolff
M
M
Fandrey
J
J
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D004921:Erythropoietin / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism*; D015846:Monokines / Q000494:pharmacology*; D051381:Rats; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D007375:Interleukin-1; D015846:Monokines; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D004921:Erythropoietin; D007371:Interferon-gamma