Growth hormone enhances thymic function in HIV-1–infected adults
Laura A. Napolitano, … , Peter Bacchetti, Joseph M. McCune
Laura A. Napolitano, … , Peter Bacchetti, Joseph M. McCune
Published February 21, 2008
Citation Information: J Clin Invest. 2008;118(3):1085-1098. https://doi.org/10.1172/JCI32830.
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Research Article

Growth hormone enhances thymic function in HIV-1–infected adults

Abstract

Growth hormone (GH) is an underappreciated but important regulator of T cell development that can reverse age-related declines in thymopoiesis in rodents. Here, we report findings of a prospective randomized study examining the effects of GH on the immune system of HIV-1–infected adults. GH treatment was associated with increased thymic mass. In addition, GH treatment enhanced thymic output, as measured by both the frequency of T cell receptor rearrangement excision circles in circulating T cells and the numbers of circulating naive and total CD4+ T cells. These findings provide compelling evidence that GH induces de novo T cell production and may, accordingly, facilitate CD4+ T cell recovery in HIV-1–infected adults. Further, these randomized, prospective data have shown that thymic involution can be pharmacologically reversed in humans, suggesting that immune-based therapies could be used to enhance thymopoiesis in immunodeficient individuals.

Authors

Laura A. Napolitano, Diane Schmidt, Michael B. Gotway, Niloufar Ameli, Erin L. Filbert, Myra M. Ng, Julie L. Clor, Lorrie Epling, Elizabeth Sinclair, Paul D. Baum, Kai Li, Marisela Lua Killian, Peter Bacchetti, Joseph M. McCune

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Figure 3

GH treatment is associated with increased thymic density and TREC frequency in HIV-1–infected adults.

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GH treatment is associated with increased thymic density and TREC freque...
(A) Comparison of changes in the GH arm versus the control arm over the first year of the study demonstrated significant increases in thymic density in GH recipients at 6 and 12 months after GH initiation. A modest, nonsignificant decrease in thymic density was observed between month 6 and month 12, commensurate with GH dose reduction and consistent with a dose-response effect of GH on the thymus. No notable changes in thymic density were seen in the absence of GH. (B) The frequency of PBMC TRECs was also increased with GH treatment during the first year of the study. (C) Comprehensive regression analysis, including crossover data of GH treatment of observational controls, demonstrates that GH treatment (circles) is associated with significant increases in thymic density and PBMC TREC frequency compared with no GH. Estimated changes with 95% CIs are displayed. Regression analysis estimated the effects of 6 months (thymic density) or 1 year (PBMC TRECs) of GH treatment compared with changes in the absence of GH. Median values are displayed in A and B. CIs and additional data are shown in Tables 2 and 3. *P < 0.05 for comparison of GH versus no GH.