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Mediators of Inflammation
Volume 2009 (2009), Article ID 489802, 7 pages
Research Article

Cardiotrophin-1 Induces Tumor Necrosis Factor Synthesis in Human Peripheral Blood Mononuclear Cells

1Division of Cardiology, Department of Internal Medicine I, Friedrich-Schiller-University of Jena, Erlanger Allee 101, 07740 Jena, Germany
2Department of Cardiology, Second Affiliated Hospital of Fujian Medical University, Zhongshan North Road 34, Quanzhou, 362000 Fujian, Germany

Received 26 May 2009; Revised 21 August 2009; Accepted 24 November 2009

Academic Editor: Charles Larry Campbell

Copyright © 2009 Michael Fritzenwanger et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Chronic heart failure (CHF) is associated with elevated concentrations of tumor necrosis factor (TNF) and cardiotrophin-1 (CT-1) and altered peripheral blood mononuclear cell (PBMC) function. Therefore, we tested whether CT-1 induces TNF in PBMC of healthy volunteers. CT-1 induced in PBMC TNF protein in the supernatant and TNF mRNA in a concentration- and time-dependent manner determined by ELISA and real-time PCR, respectively. Maximal TNF protein was achieved with 100 ng/mL CT-1 after 3–6 hours and maximal TNF mRNA induction after 1 hour. ELISA data were confirmed using immunofluorescent flow cytometry. Inhibitor studies with actinomycin D and brefeldin A showed that both protein synthesis and intracellular transport are essential for CT-1 induced TNF expression. CT-1 caused a dose dependent nuclear factor (NF) B translocation. Parthenolide inhibited both NF B translocation and TNF protein expression indicating that NF B seems to be necessary. We revealed a new mechanism for elevated serum TNF concentrations and PBMC activation in CHF besides the hypothesis of PBMC activation by bacterial translocation from the gut.