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Alterations of monocyte function in patients with growth hormone (GH) deficiency: effect of substitutive GH therapy
O Serri1, P St-Jacques, M Sartippour
1Centre Hospitalier de l'Université de Montréal Research Center, and Department of Nutrition, University of Montreal, Quebec, Canada.
Insights
Growth hormone deficiency (GHD) increases monocyte activation and cardiovascular risk. GH replacement therapy partially reduces this activation, potentially lowering cardiovascular event risk in GHD patients.
Area of Science:
- Endocrinology
- Immunology
- Cardiovascular Science
Background:
- Growth hormone deficiency (GHD) is linked to higher rates of atherosclerosis and cardiovascular disease.
- Monocytes are key players in the development of atherosclerosis.
Purpose of the Study:
- To investigate the impact of GHD and GH replacement therapy on monocyte function.
- To assess changes in cytokine levels and monocyte adhesion in hypopituitary subjects.
Main Methods:
- Twelve hypopituitary patients with GHD received GH replacement therapy for 3 months.
- Plasma cytokine levels (TNF-alpha, IL-6), monocyte cytokine production, and monocyte adhesion to endothelial cells were measured before and after treatment.
- Control groups were used for comparison.
Main Results:
- Patients with GHD exhibited elevated basal plasma and monocyte production of TNF-alpha and IL-6 compared to controls.
- GH therapy significantly reduced plasma and monocyte TNF-alpha levels and monocyte IL-6 production.
- Monocyte adhesion to endothelial cells remained elevated despite GH treatment.
Conclusions:
- GHD is associated with increased monocyte activation, indicated by elevated cytokine levels and production.
- GH replacement therapy partially ameliorates these markers of monocyte activation.
- Reducing monocyte activation via GH therapy may help decrease cardiovascular risk in GHD patients.
Abstract:
GH deficiency (GHD) is associated with increased prevalence of atherosclerosis and cardiovascular morbidity. Because monocytes play a crucial role in the development of atherosclerosis, we investigated in the present study the effect of GH deficiency and subsequent GH replacement on monocytic function in hypopituitary subjects. Twelve patients were randomized to receive GH replacement therapy (either 3 or 6 microg/kg x day, s.c.) for 3 months. Plasma levels and monocyte production of cytokines and monocyte adhesion to endothelium 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. Basal monocyte production of both cytokines was also significantly higher in patients with GHD [484% over control values for TNF alpha (P = 0.0007); 1479% 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, pre- vs. post-GH therapy), monocyte TNF alpha production (204% over control values; P = 0.01), plasma IL-6 (219% over control values; P = 0.07), and monocyte IL-6 production (448% over control values; P = 0.01). Plasma TNF alpha levels positively correlated with monocyte TNF alpha production in patients with GHD both before and after GH therapy (P = 0.003 and P = 0.049, respectively). A positive correlation (P = 0.0003) was also observed between monocyte TNF alpha production and monocyte IL-6 production. There were no correlations between these plasma cytokine levels or monocyte cytokine production and parameters of body composition, lipid profile, or IGF-I and IGF-binding protein-3 levels. Before GH treatment, adhesiveness of monocytes to cultured aortic endothelial cells was also enhanced. This alteration was not reversed by GH administration. In conclusion, our results demonstrate that markers of monocyte activation are increased in patients with GHD and that GH replacement partly reduces these abnormalities. Reduction of cellular activation of monocytes by GH therapy could potentially contribute to reduce the risk of cardiovascular events in patients with GHD.