title: Effects of growth hormone on circulating cytokine network, and left ventricular contractile performance and geometry in patients with idiopathic dilated cardiomyopathy.
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-alpha (TNF-alpha), 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-beta2 (TGF-beta2) 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-alpha (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-alpha (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-beta2/TNF-alpha (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/cm(2), 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*cm(2)/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-alpha (r=0.69, P=0.011) and TGF-beta2/TNF-alpha (r=0.58, P=0.046) ratios, as well as the reduction in plasma TNF-alpha 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.
authors.affiliation: Second Department of Cardiovascular Medicine, Onassis Cardiac Surgery Center, Athens, Greece. sadamo@bigfoot.com
authors.forename: Stamatis
authors.initials: S
authors.lastname: Adamopoulos
authors.forename: John T
authors.initials: JT
authors.lastname: Parissis
authors.forename: Ioannis
authors.initials: I
authors.lastname: Paraskevaidis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karatzas
authors.forename: Efthimios
authors.initials: E
authors.lastname: Livanis
authors.forename: Michael
authors.initials: M
authors.lastname: Georgiadis
authors.forename: George
authors.initials: G
authors.lastname: Karavolias
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Mitropoulos
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Degiannis
authors.forename: Dimitrios Th
authors.initials: DT
authors.lastname: Kremastinos
mesh_terms: D000704:Analysis of Variance; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D016207:Cytokines / Q000097:blood*; D005080:Exercise Test; D017079:Exercise Tolerance; D005260:Female; D013006:Growth Hormone / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D016207:Cytokines; D013006:Growth Hormone