ArticleMolecular medicine (Cambridge, Mass.)2020
Correction of immunosuppression in aged septic rats by human ghrelin and growth hormone through the vagus nerve-dependent inhibition of TGF-β production.
Article in Molecular medicine (Cambridge, Mass.), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 13 citations in OpenAlex.
- Beyond Hunger: The Structure, Signaling, and Systemic Roles of Ghrelin.International journal of molecular sciences · 2025Review
- Mental distress and inflammation in bladder cancer: The nerve makes things less vague.Brain, behavior, & immunity - health · 2025Article
- Recent advances in targeting obesity, with a focus on TGF-β signaling and vagus nerve innervation.Bioelectronic medicine · 2025Review
- Gut microbiota and sepsis-associated encephalopathy: pathogenesis and precision therapies.Frontiers in neuroscience · 2025Review
- Exploring the Antifibrotic Mechanisms of Ghrelin: Modulating TGF-β Signalling in Organ Fibrosis.Expert reviews in molecular medicine · 2024Review
- Lipid Fraction fromAntioxidants (Basel, Switzerland) · 2024Article
- The implication of targeting PD-1:PD-L1 pathway in treating sepsis through immunostimulatory and anti-inflammatory pathways.Frontiers in immunology · 2023Review
- The liver in sepsis: molecular mechanism of liver failure and their potential for clinical translation.Molecular medicine (Cambridge, Mass.) · 2022Review
- Growth hormone associated with treatment efficacy of immune checkpoint inhibitors in gastric cancer patients.Frontiers in oncology · 2022Article
- Therapeutic Potential of Vagus Nerve Stimulation for Inflammatory Bowel Diseases.Frontiers in neuroscience · 2021Review
- Ghrelin as an Anti-Sepsis Peptide: Review.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundCo-administration of human ghrelin and growth hormone (GH) reverse immunosuppression in septic aged animals, but the mechanism remains elusive. Here, we hypothesize that ghrelin and GH co-treatment restores the immune response in aged septic rats by inhibiting the production of transforming growth factor-β (TGF-β), an immunoregulatory cytokine, through the vagus nerve.
methodsMale aged Fischer rats (22-23-month-old) were made septic by cecal ligation and puncture (CLP) with or without dissecting the vagus nerve (vagotomy). Human ghrelin and GH or vehicle (PBS) were administrated subcutaneously at 5 h post CLP. After 20 h of CLP, serum and spleens were harvested.
resultsSerum TGF-β levels were increased in septic aged rats, while ghrelin and GH treatment significantly reduced its levels. Expression of TGF-β in the spleen was upregulated after sepsis, while ghrelin and GH treatment significantly inhibited its expression. TNF-α and IL-6 levels were significantly reduced after ex vivo LPS stimulation of splenocytes from rats that underwent CLP compared to sham rats; while these levels were significantly higher in splenocytes from ghrelin and GH-treated CLP rats compared to vehicle-treated CLP rats. Ghrelin and GH treatment reduced program death receptor-1 (PD-1) expression, increased human leukocyte antigen-DR (HLA-DR) expression, attenuated lymphopenia, and cleaved caspase-3 levels in the spleen of septic aged rats. Vagotomy diminished the beneficial effects of ghrelin and GH treatment in septic rats. In vitro, the addition of ghrelin, GH, or ghrelin and GH together had no effect on restoring immune response in splenocytes from CLP rats following LPS stimulation, indicating the requirement of the vagus nerve for ghrelin and GH's effect.
conclusionsGhrelin and GH attenuate immunosuppression in aged septic rats through the vagus nerve-dependent inhibition of TGF-β production.
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