Muscular levels of proinflammatory cytokines correlate with a reduced expression of insulinlike growth factor-I in chronic heart failure

Objective: Chronic heart failure (CHF) is associated with metabolic abnormalities leading to a catabolic syndrome in advanced stages of the disease. To assess the role of proinflammatory cytokines for the local expression of insulin-like growth factor-I (IGF-I) in this process, muscular and systemic levels of interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNFα) and IGF-I were analyzed in an animal model of CHF. Methods: Ligation of the left coronary artery or sham operation was performed in adult Wistar Kyoto rats. After 12 weeks, all animals were assessed by echocardiography and cardiac catheterization. Serum levels of IGF-I, IL-1β, TNFα and IL-6 were determined by ELISA. In the quadriceps muscle, the expression of IGF-I, IGF-I receptor, IL-1β and TNFα were assessed by RT-PCR and quantitative immunohistochemistry. Alterations in muscle fiber morphology were analyzed microscopically. Results: The local expression of IGF-I decreased significantly in animals with CHF (0.47 ± 0.07 versus 0.77 ± 0.09; p < 0.01). This reduction correlated with a decreased muscle fiber cross-sectional area (r = 0.62; p < 0.01) and inversely with the local expression of IL-1β (r = −0.49; p < 0.05). IGF-I serum levels showed no significant differences between the two groups. Conclusions: In CHF, the local IGF-I expression is reduced in the presence of normal serum levels of IGF-I. Both elevated proinflammatory cytokines and reduced local IGF-I expression contribute to a catabolic metabolism that may finally result in skeletal muscle atrophy and cardiac cachexia.

Authors and Affiliations

1. Cardiovascular Research, Partners Research Facility, 65 Landsdowne St., Room 289, Cambridge, MA 02139, USA. pcschulze@rics.bwh.harvard.edu, , , , , , US

   P. Christian Schulze

2. University of Leipzig, Heart Center, Department of Cardiology, Strümpellstr. 39, 04289 Leipzig, Germany, , , , , , DE

   Stephan Gielen, Volker Adams, Axel Linke, Sven Möbius-Winkler, Sandra Erbs, Rainer Hambrecht & Gerhard Schuler

3. University of Leipzig, Institut of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, Liebigstr. 27a, 04103 Leipzig, Germany, , , , , , DE

   Jürgen Kratzsch

Received: 17 December 2002, Returned for 1. revision: 13 January 2003, 1. Revision received: 28 January 2003, Returned for 2. revision: 10 February 2003, 2. Revision received: 10 March 2003, Accepted: 11 March 2003, Published online: 16 April 2003

Drs. Schulze and Gielen, Both contributed equally to this work

Correspondence to: P. C. Schulze, MD

Reprints and permissions