التفاصيل البيبلوغرافية
| العنوان: |
Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-infection and Nonalcoholic Fatty Liver Disease. |
| المؤلفون: |
Stanley, Takara L, Fourman, Lindsay T, Wong, Lai Ping, Sadreyev, Ruslan, Billingsley, James M, Feldpausch, Meghan N, Zheng, Isabel, Pan, Chelsea S, Boutin, Autumn, Lee, Hang, Corey, Kathleen E, Torriani, Martin, Kleiner, David E, Chung, Raymond T, Hadigan, Colleen M, Grinspoon, Steven K |
| المصدر: |
Clinical Infectious Diseases; 8/15/2021, Vol. 73 Issue 4, p621-630, 10p |
| مصطلحات موضوعية: |
PITUITARY hormone releasing factors, BIOMARKERS, HIV-positive persons, BIOPSY, LIVER, FATTY liver, BLOOD plasma, IMMUNE system, CELL physiology, PROTEOMICS, HUMAN growth hormone, TREATMENT effectiveness, RANDOMIZED controlled trials, PLACEBOS, GENE expression profiling, IMMUNITY, BLIND experiment, T cells, CHEMOKINES, MONOCYTES, EVALUATION |
| مستخلص: |
Background The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis modulates critical metabolic pathways; however, little is known regarding effects of augmenting pulsatile GH secretion on immune function in humans. This study used proteomics and gene set enrichment analysis to assess effects of a GH releasing hormone (GHRH) analog, tesamorelin, on circulating immune markers and liver tissue in people with human immunodeficiency virus (HIV) (PWH) and nonalcoholic fatty liver disease (NAFLD). Methods 92 biomarkers associated with immunity, chemotaxis, and metabolism were measured in plasma samples from 61 PWH with NAFLD who participated in a double-blind, randomized trial of tesamorelin versus placebo for 12 months. Gene set enrichment analysis was performed on serial liver biopsies targeted to immune pathways. Results Tesamorelin, compared to placebo, decreased interconnected proteins related to cytotoxic T-cell and monocyte activation. Circulating concentrations of 13 proteins were significantly decreased, and no proteins increased, by tesamorelin. These included 4 chemokines (CCL3, CCL4, CCL13 [MCP4], IL8 [CXCL8]), 2 cytokines (IL-10 and CSF-1), and 4 T-cell associated molecules (CD8A, CRTAM, GZMA, ADGRG1), as well as ARG1, Gal-9, and HGF. Network analysis indicated close interaction among the gene pathways responsible for these proteins, with imputational analyses suggesting down-regulation of a closely related cluster of immune pathways. Targeted transcriptomics using liver tissue confirmed a significant end-organ signal of down-regulated immune activation pathways. Conclusions Long-term treatment with a GHRH analog reduced markers of T-cell and monocyte/macrophage activity, suggesting that augmentation of the GH axis may ameliorate immune activation in an HIV population with metabolic dysregulation, systemic and end organ inflammation. Clinical Trials Registration. NCT02196831. [ABSTRACT FROM AUTHOR] |
|
Copyright of Clinical Infectious Diseases is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
