Growth hormone administration reduces circulating proinflammatory cytokines and soluble Fas/soluble Fas ligand system in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy

Abstract

Background Recent studies have shown that an abnormal proinflammatory cytokine expression and apoptotic process contribute to adverse left ventricular remodeling and progress of chronic heart failure. This study investigates the effects of growth hormone (GH) administration on serum levels of representative proinflammatory cytokines and soluble apoptosis mediators in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy (IDC). Methods Serum levels of tumor necrosis factor-α (TNF-α), its soluble receptors (sTNF-RI, sTNF-RII), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), soluble Fas (sFas) and soluble Fas Ligand (sFasL) were determined (enzyme-linked immunosorbent assay method) in 10 patients with IDC (New York Heart Association class III, ejection fraction 24% ± 2%) before and after a 3-month subcutaneous administration of 4 IU GH every other day (randomized crossover design). Peak oxygen consumption (Vo2max) was also used to evaluate the functional status of patients with IDC. Results Treatment with GH produced a significant reduction in serum levels of TNF-α (8.2 ± 1.2 vs 5.7 ± 1.1 pg/mL, P <.05), sTNF-RI (3.9 ± 0.4 vs 3.2 ± 0.3 ng/mL, P <.05), sTNF-RII (2.6 ± 0.3 vs 2.2 ± 0.2 ng/mL, P <.05), IL-6 (5.5 ± 0.6 vs 4.4 ± 0.4 pg/mL, P =.05), sIL-6R (32.7 ± 3.0 vs 28.2 ± 3.0 ng/mL, P <.05), sFas (4.4 ± 0.8 vs 3.1 ± 0.6 ng/mL, P <.05), and sFasL (34.2 ± 11.7 vs 18.8 ± 7.3 pg/mL, P <.01). A significant improvement was also observed in Vo2max after the completion of 3 months' treatment with GH (15.0 ± 0.8 vs 17.2 ± 1.0 mL/kg/min, P <.05). Good correlations were found between GH-induced reduction in TNF-α levels and increase in Vo2max (r = −0.64, P <.05) as well as between GH-induced reduction in sFasL and increase in Vo2max (r = −0.56, P =.08). Conclusions GH administration reduces serum levels of proinflammatory cytokines and soluble Fas/FasL system in patients with IDC. These immunomodulatory effects may be associated with improvement in clinical performance and exercise capacity of patients with IDC. (Am Heart J 2002;144:359-64.)