Pleiotropic modulation of thymic functions by growth hormone: from physiology to therapy.
In the context of the cross-talk between the neuroendocrine and immune systems, it is well known that growth hormone (GH) exerts physiological effects in central as well as peripheral compartments of the immune system. GH modulates a variety of thymic functions, including proliferation of thymocytes and thymic epithelial cells (TEC). Accordingly, GH-transgenic mice, as well as animals and humans treated with exogenous GH, exhibit an enhanced cellularity in the organ. GH also stimulates the secretion of cytokines and chemokines by the thymic microenvironment, as well as the production of extracellular matrix proteins. These effects lead to an increase in thymocyte migratory responses and intrathymic traffic of developing T cells, including the export of thymocytes from the organ, as ascertained by experimental studies with intrathymic injection of GH in normal mice and with GH-transgenic animals. Most likely, GH effects in the thymus are mediated by an IGF-1/IGF-1 receptor circuitry, which physiologically operates in nonstimulated conditions in both thymocytes and TECs. Since GH enhances thymus replenishment and increases intrathymic T-cell traffic, ultimately modulating thymocyte exit, it should be placed as a potential adjuvant therapeutic agent in the treatment of immunodeficiencies associated with thymic atrophy, and examples recently appeared in the literature are promising and strongly indicate that GH can be beneficial for individuals suffering severe immunodeficiency.
Savino
Wilson
W
Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Ave. Brasil 4365, 21045-900 Rio de Janeiro, Brazil. savino@fiocruz.br
Dardenne
Mireille
M
D000818:Animals; D004847:Epithelial Cells / Q000502:physiology; D019672:Genes, T-Cell Receptor / Q000502:physiology; D013006:Growth Hormone / Q000502:physiology*; D019382:Human Growth Hormone / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D015213:Neuroimmunomodulation; D017526:Receptor, IGF Type 1 / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000502:physiology*
D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1