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.
Stanley. Takara L TL; Fourman. Lindsay T LT; Wong. Lai Ping LP; Sadreyev. Ruslan R; Billingsley. James M JM; Feldpausch. Meghan N MN; Zheng. Isabel I; Pan. Chelsea S CS; Boutin. Autumn A; Lee. Hang H; Corey. Kathleen E KE; Torriani. Martin M; Kleiner. David E DE; Chung. Raymond T RT; Hadigan. Colleen M CM; Grinspoon. Steven K SK
Key Findings
- Tesamorelin reduced 13 circulating immune‑related proteins (including chemokines CCL3, CCL4, CCL13, IL‑8, cytokines IL‑10 and CSF‑1, and T‑cell markers CD8A, CRTAM, GZMA, ADGRG1).
- No immune proteins were increased; the overall network of immune pathways was down‑regulated.
- Liver biopsy transcriptomics confirmed a matching decrease in immune‑activation gene pathways.
Practical Outcomes
- For biohackers interested in anti‑inflammatory or immune‑modulating strategies, tesamorelin shows promise as a tool that may dampen chronic immune activation, especially in metabolic disease contexts. However, the data come from a specific HIV‑positive, NAFLD cohort, and the drug requires a prescription and careful monitoring, so it is not a ready‑to‑use supplement but a candidate for further investigation in broader longevity protocols.
Summary
In a 12‑month trial, the growth‑hormone‑releasing hormone drug tesamorelin lowered several blood proteins that signal T‑cell and monocyte activity, indicating reduced immune activation. The effect was seen in people with HIV and fatty liver disease, and liver tissue also showed fewer inflammatory signals.
Abstract
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). 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. 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. 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.
Study Information
pubmed
2021
2021-08-16T00:00:00.000Z
10.1093/cid/ciab019
9
48