This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Serri, O. Articles by Renier, G. Search for Related Content PubMed PubMed Citation Articles by Serri, O. Articles by Renier, G.

Alterations of Monocyte Function in Patients with Growth Hormone (GH) Deficiency: Effect of Substitutive GH Therapy¹

Metabolic Unit, Centre Hospitalier de l’Université de Montréal Research Center, Notre Dame Pavilion, and the Department of Nutrition, University of Montreal, Montreal, Quebec, Canada H2L 4M1

Address all correspondence and requests for reprints to: Dr. Gene-viève Renier, Centre Hospitalier de l’Université de Montréal Research Center, Notre Dame Pavilion, 3rd floor, J. A. de Sève, Y-3622, 1560 Sherbrooke Street East, Montreal, Quebec, Canada H2L 4M1. E-mail: renierg{at}ere.umontreal.ca

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 µg/kg·day, sc) 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- (TNF; 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 (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 (135% over control values; P = 0.03, pre- vs. post-GH therapy), monocyte TNF 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 levels positively correlated with monocyte TNF 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 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.

This article has been cited by other articles:

				C. Beauregard, A. L. Utz, A. E. Schaub, L. Nachtigall, B. M. K. Biller, K. K. Miller, and A. Klibanski Growth Hormone Decreases Visceral Fat and Improves Cardiovascular Risk Markers in Women with Hypopituitarism: A Randomized, Placebo-Controlled Study J. Clin. Endocrinol. Metab., June 1, 2008; 93(6): 2063 - 2071. [Abstract] [Full Text] [PDF]

				M. A. Schrager, E. J. Metter, E. Simonsick, A. Ble, S. Bandinelli, F. Lauretani, and L. Ferrucci Sarcopenic obesity and inflammation in the InCHIANTI study J Appl Physiol, March 1, 2007; 102(3): 919 - 925. [Abstract] [Full Text] [PDF]

				E. R Christ, M. H Cummings, M. Stolinski, N. Jackson, P. J Lumb, A. S Wierzbicki, P. H Sonksen, D. L Russell-Jones, and A M. Umpleby Low-density lipoprotein apolipoprotein B100 turnover in hypopituitary patients with GH deficiency: a stable isotope study. Eur. J. Endocrinol., March 1, 2006; 154(3): 459 - 466. [Abstract] [Full Text] [PDF]

				S. Pagani, C. Meazza, P. Travaglino, F. De Benedetti, C. Tinelli, and M. Bozzola Serum cytokine levels in GH-deficient children during substitutive GH therapy Eur. J. Endocrinol., February 1, 2005; 152(2): 207 - 210. [Abstract] [Full Text] [PDF]

				K.-C. Leung, G. Johannsson, G. M. Leong, and K. K. Y. Ho Estrogen Regulation of Growth Hormone Action Endocr. Rev., October 1, 2004; 25(5): 693 - 721. [Abstract] [Full Text] [PDF]

				O. Serri, L. Li, F. Maingrette, N. Jaffry, and G. Renier Enhanced Lipoprotein Lipase Secretion and Foam Cell Formation by Macrophages of Patients with Growth Hormone Deficiency: Possible Contribution to Increased Risk of Atherogenesis? J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 979 - 985. [Abstract] [Full Text] [PDF]

				A. R. Cappola, Q.-L. Xue, L. Ferrucci, J. M. Guralnik, S. Volpato, and L. P. Fried Insulin-Like Growth Factor I and Interleukin-6 Contribute Synergistically to Disability and Mortality in Older Women J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2019 - 2025. [Abstract] [Full Text] [PDF]

				D. M. Cook Shouldn't Adults with Growth Hormone Deficiency Be Offered Growth Hormone Replacement Therapy? Ann Intern Med, August 6, 2002; 137(3): 197 - 201. [Abstract] [Full Text] [PDF]

				G. Sesmilo, W. P. Fairfield, L. Katznelson, K. Pulaski, P. U. Freda, V. Bonert, E. Dimaraki, S. Stavrou, M. L. Vance, D. Hayden, et al. Cardiovascular Risk Factors in Acromegaly before and after Normalization of Serum IGF-I Levels with the GH Antagonist Pegvisomant J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1692 - 1699. [Abstract] [Full Text] [PDF]

				D. S. Hardin, K. J. Ellis, M. Dyson, J. Rice, R. McConnell, and D. K. Seilheimer Growth Hormone Decreases Protein Catabolism in Children with Cystic Fibrosis J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4424 - 4428. [Abstract] [Full Text] [PDF]

				S. H. Zarkesh-Esfahani, O. Kolstad, R. A. Metcalfe, P. F. Watson, S. Von Laue, S. Walters, A. Revhaug, A. P. Weetman, and R. J. M. Ross High-Dose Growth Hormone Does Not Affect Proinflammatory Cytokine (Tumor Necrosis Factor-{alpha}, Interleukin-6, and Interferon-{gamma}) Release from Activated Peripheral Blood Mononuclear Cells or after Minimal to Moderate Surgical Stress J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3383 - 3390. [Abstract] [Full Text]

				G. Sesmilo, B. M.K. Biller, J. Llevadot, D. Hayden, G. Hanson, N. Rifai, and A. Klibanski Effects of Growth Hormone Administration on Inflammatory and Other Cardiovascular Risk Markers in Men with Growth Hormone Deficiency: A Randomized, Controlled Clinical Trial Ann Intern Med, July 18, 2000; 133(2): 111 - 122. [Abstract] [Full Text] [PDF]

				T. Elhadd, T. Abdu, R. Clayton, and J. Belch Comment on Alteration of monocyte function in patients with growth hormone deficiency: Effect of substitutive GH therapy J. Clin. Endocrinol. Metab., September 1, 1999; 84(9): 3405a - 3406. [Full Text]