Tumor necrosis factor α (TNFα), via ITS 55 kDa receptor, exerts an autocrine inhibition of hepatic erythropoietin (Epo) synthesis

W. Jelkmann*

*Corresponding author for this work
1 Citation (Scopus)


The recent demonstration of TNFa in hepatocytes of hepatitis virus-infected patients prompted us to study whether TNFa is an autocrine inhibitor of hepatic Epo synthesis. Using human hepatoma cells (HepG2) as an in vitro model, we tested whether (a) TNFa receptor-specific mutants suppress Epo production, (b) hepatic TNFa gene expression is induced by other proinflammatory interteukins (IL-1, 11-6) and phorbol ester (PMA), and (c) antisera towards TNFa abolish the inhibition of Epo production exerted by TNFa, IL-1 or PMA. We found that (a) a TNFR-p55-specific mutant (concentration needed for halfmaximal inhibition, 1C. 1 ng/ml) lowered Epo production similar to recombinant human wild type TNFa, while a TNFR-p75-specific mutant was ineffective up to 100 ng/ml (b) No constitutive TNFa gene expression was detected by quantitative RT-PCR IL-1J3 (300 pg/ml) or PMA (100 nM) produced a marked increase in TNFa mRNA levels, being maximal after 3 h of incubation. il-6 (200 pg/ml) was without effect in this respect. IL-1 p and PMA also stimulated the secretion of immunoreactive TNFa, which was associated with a decrease in Epo secretion, (c) The addition of antiserum to TNFa restored the capacity for Epo production in cultures treated with TNFa or TNFR-p55-spedfic mutant and partially reversed the inhibition exerted by IL-1[1 and PMA. These findings show that TNFa suppresses hepatic production of Epo via the 55 kDa receptor. In addition, the hypothesis is supported that the local production of TNFa, induced by cytokines such as IL-1, plays an important role in the impaired hepatic synthesis of Epo in inflammatory diseases.

Original languageEnglish
JournalExperimental Hematology
Issue number9
Pages (from-to)1097
Number of pages1
Publication statusPublished - 1996

Research Areas and Centers

  • Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)


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