Alterations of monocyte function in patients with growth hormone (GH) deficiency: Effect of substitutive GH therapy

GH deficiency (GHD) is associated with increased prevalence of atherosclero sis and cardiovascular morbidity. Because monocytes play a crucial role in the development of atherosclerosis, we investigated in the present study th e effect of GH deficiency and subsequent GH replacement on monocytic functi on in hypopituitary subjects. Twelve patients were randomized to receive GK replacement therapy (either 3 or 6 mu g/kg day, sc) far 3 months. Plasma l evels and monocyte production of cytokines and monocyte adhesion to endothe lium were determined in controls and patients with GHD before and after GH treatment. Before GH therapy, patients with GHD had increased basal plasma tumor necrosis factor-alpha (TNF alpha; 220% over control values; P = 0.004 ) and interleukin-6 (IL-6; 340% over control values; P = 0.0009) levels. Ba sal monocyte production of both cytokines was also significantly higher in patients with GHD [484% over control values for TNF alpha (P = 0.0007); 147 9% over control values for IL-6 (P = 0.035)]. GH treatment for 3 months led to a reduction in plasma TNF alpha (135% over control values; P = 0.03, pr e- vs. post-GH therapy), monocyte TNF alpha production (204% over control v alues; P = 0.01), plasma IL-6 (219% over control values; P = 0.07), and mon ocyte IL-6 production (448% over control values; P = 0.01). Plasma TNF alph a levels positively correlated with monocyte TNF alpha production in patien ts with GHD both before and after GH therapy (P = 0.003 and P = 0.049, resp ectively). A positive correlation (P = 0.0003) was also observed between mo nocyte TNF alpha production and monocyte IL-6 production. There were no cor relations between these plasma cytokine levels or monocyte cytokine product ion and parameters of body composition, lipid profile, or IGF-I and TGF-bin ding protein-3 levels. Before GH treatment, adhesiveness of monocytes to cu ltured aortic endothelial cells was also enhanced. This alteration was not reversed by GH administration. In conclusion, our results demonstrate that marker; of monocyte activation are increased in patients with GHD and that GH replacement partly reduces these abnormalities. Reduction of cellular ac tivation of monocytes by GH therapy could potentially contribute to reduce the risk of cardiovascular events in patients with GHD.