Copyright © 2003 by the European Society of Cardiology.
Clinical research
Effects of growth hormone on circulating cytokine network, and left ventricular contractile performance and geometry in patients with idiopathic dilated cardiomyopathy
Second Department of Cardiovascular Medicine, Onassis Cardiac Surgery Center, Athens, Greece
* Correspondence to: Stamatis Adamopoulos, MD, PhD (London), FESC, Zinonos 9, 15234 Halandri, Athens, Greece. Tel: +30-210-6848463; Fax: +30-210-9493373
E-mail address: sadamo{at}bigfoot.com
Received 17 April 2003; revised 19 July 2003; accepted 31 July 2003
Abstract
Background Recent experimental and clinical data indicate that abnormal central and peripheral immune reactions contribute to the progression of chronic heart failure, and that immunomodulation may be an important therapeutic approach in this syndrome.
Aims We sought to study the effects of growth hormone (GH) administration on circulating pro-inflammatory/anti-inflammatory cytokine balance, and to investigate whether these GH-induced immunomodulatory effects are associated with the improvement of left ventricular (LV) contractile performance in idiopathic dilated cardiomyopathy (DCM) patients.
Methods Plasma pro-inflammatory cytokines tumour necrosis factor-
(TNF-), interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF) and its soluble receptor (sGM-CSFR), chemotactic cytokine macrophage chemoattractant protein-1 (MCP-1), soluble adhesion molecules intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1), and, finally, anti-inflammatory cytokines interleukin-10 (IL-10) and transforming growth factor-ß2 (TGF-ß2) were measured (ELISA method) in 12 patients with DCM (NYHA class III; LV ejection fraction: 23.6±1.7%) before and after a 3-month subcutaneous administration of GH 4IU every other day (randomized crossover design). Peak oxygen uptake (VO2 max), LV dimensions, LV mass index, end-systolic wall stress (ESWS), mean velocity of circumferential fibre shortening (Vcfc), and contractile reserve (change of ratio Vcfc/ESWS after dobutamine administration) were also determined at the same period.
Results Treatment with GH produced a significant reduction in plasma TNF- (7.8±1.1 vs 5.5±0.9pg/ml, P=0.013), IL-6 (5.7±0.5 vs 4.7±0.4pg/ml, P=0.043), GM-CSF (27.3±1.7 vs 23.3±1.8pg/ml, P=0.042), sGM-CSFR (4.0±0.4 vs 3.2±0.4ng/ml, P=0.039), MCP-1 (199±5 vs 184±6pg/ml, P=0.048), sICAM-1 (324±34 vs 274±27ng/ml, P=0.008) and sVCAM-1 (1238±89 vs 1043±77ng/ml, P=0.002) in DCM patients. A significant increase in ratios IL-10/TNF- (1.9±0.3 vs 3.5±0.9, P=0.049), IL-10/IL-6(2.6±0.6 vs 3.2±0.5, P=0.044) and TGF-ß2/TNF- (3.1±0.6 vs 4.4±0.6, P=0.05) was alsofound with GH therapy. A significant reduction in ESWS (841±62 vs 634±48gr/cm2, P=0.0026) and LV end-systolic volume index (LVESVI, 128±12 vs 102±12ml, P=0.035) as well as a significant increase in posterior wall thickness (PWTH, 9.2±0.5 vs 10.3±0.6mm, P=0.034), contractile reserve (0.00029±0.0001 vs 0.00054±0.0001circ*cm2/gr*s, P=0.00028) and VO2max (15.3±0.7 vs 17.1±0.9ml/kg/min, P=0.002) were observed after GH administration. Good correlations were found between GH-induced increase in contractile reserve and the increases in VO2max (r=0.63, P=0.028), IL-10/TNF- (r=0.69, P=0.011) and TGF-ß2/TNF- (r=0.58, P=0.046) ratios, as well as the reduction in plasma TNF- levels (r=–0.86, P=0.0004).
Conclusions GH administration modulates beneficially circulating cytokine network and soluble adhesion molecules in patients with DCM, whilst enhancing contractile reserve and diminishing LV volumes. These GH-induced anti-inflammatory effects may be associated with the improvement in LV contractile performance and exercise capacity as well as with the reverse of LV remodelling of patients with DCM.
Key Words: Cytokines • Adhesion molecules • Inflammation • Growth hormone • Contractile performance • Cardiac remodelling • Dilated cardiomyopathy • Chronic heart failure
CiteULike 
Connotea 
Del.icio.us What's this?
Related articles in EHJ:
- Growth hormone and proinflammatory cytokine activation in heart failure: Just a new verse to an old sirens’ song?
- Kai C Wollert and Helmut Drexler
EHJ 2003 24: 2164-2165.[Extract] [Full Text]
This article has been cited by other articles:
|
|
 |
|
  S. Fazio, E. A. Palmieri, F. Affuso, A. Cittadini, G. Castellano, T. Russo, A. Ruvolo, R. Napoli, and L. Sacca Effects of Growth Hormone on Exercise Capacity and Cardiopulmonary Performance in Patients with Chronic Heart Failure J. Clin. Endocrinol. Metab., November 1, 2007; 92(11): 4218 - 4223. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Piccoli, L. Degen, C. MacLean, S. Peter, L. Baselgia, F. Larsen, C. Beglinger, and J. Drewe Pharmacokinetics and Pharmacodynamic Effects of an Oral Ghrelin Agonist in Healthy Subjects J. Clin. Endocrinol. Metab., May 1, 2007; 92(5): 1814 - 1820. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Raphael, C. Briscoe, J. Davies, Z. Ian Whinnett, C. Manisty, R. Sutton, J. Mayet, and D. P Francis Limitations of the New York Heart Association functional classification system and self-reported walking distances in chronic heart failure Heart, April 1, 2007; 93(4): 476 - 482. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Le Corvoisier, L. Hittinger, P. Chanson, O. Montagne, I. Macquin-Mavier, and P. Maison Cardiac Effects of Growth Hormone Treatment in Chronic Heart Failure: A Meta-Analysis J. Clin. Endocrinol. Metab., January 1, 2007; 92(1): 180 - 185. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kaur, A. K. Sharma, and P. K. Singal Significance of changes in TNF-{alpha} and IL-10 levels in the progression of heart failure subsequent to myocardial infarction Am J Physiol Heart Circ Physiol, July 1, 2006; 291(1): H106 - H113. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. E. Lipshultz, S. A. Vlach, S. R. Lipsitz, S. E. Sallan, M. L. Schwartz, and S. D. Colan Cardiac Changes Associated With Growth Hormone Therapy Among Children Treated With Anthracyclines Pediatrics, June 1, 2005; 115(6): 1613 - 1622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Dreifuss Cardiac Effects of Growth Hormone Circulation, June 29, 2004; 109(25): e332 - e332. [Full Text] [PDF]
|
|
|
|
 |
|
 K. C Wollert and H. Drexler Growth hormone and proinflammatory cytokine activation in heart failure: Just a new verse to an old sirens' song? Eur. Heart J., December 2, 2003; 24(24): 2164 - 2165. [Full Text] [PDF]
|
|