Article

Dixit, V. D. et al. Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J. Clin. Invest. 114, 57-66

Morehouse School of Medicine, Atlanta, Georgia, United States
Journal of Clinical Investigation (Impact Factor: 13.22). 08/2004; 114(1):57-66. DOI: 10.1172/JCI21134
Source: PubMed

ABSTRACT

Ghrelin, a recently described endogenous ligand for the growth hormone secretagogue receptor (GHS-R), is produced by stomach cells and is a potent circulating orexigen, controlling energy expenditure, adiposity, and growth hormone secretion. However, the functional role of ghrelin in regulation of immune responses remains undefined. Here we report that GHS-R and ghrelin are expressed in human T lymphocytes and monocytes, where ghrelin acts via GHS-R to specifically inhibit the expression of proinflammatory anorectic cytokines such as IL-1beta, IL-6, and TNF-alpha. Ghrelin led to a dose-dependent inhibition of leptin-induced cytokine expression, while leptin upregulated GHS-R expression on human T lymphocytes. These data suggest the existence of a reciprocal regulatory network by which ghrelin and leptin control immune cell activation and inflammation. Moreover, ghrelin also exerts potent anti-inflammatory effects and attenuates endotoxin-induced anorexia in a murine endotoxemia model. We believe this to be the first report demonstrating that ghrelin functions as a key signal, coupling the metabolic axis to the immune system, and supporting the potential use of ghrelin and GHS-R agonists in the management of disease-associated cachexia.

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    • "Stomach produces ghrelin and its receptor is present also on T cells and monocytes, where the circulating orexin inhibits the expression of pro-inflammatory cytokines. Ghrelin leads to a dose-dependent inhibition of leptininduced cytokines and leptin itself increases ghrelin receptors on T lymphocytes [165]. This hormonal/immune network between ghrelin and leptin contributes to regulate the balance between effector and tolerant immune response and involves also calcitriol as an effector hormone. "
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    • "Stomach produces ghrelin and its receptor is present also on T cells and monocytes, where the circulating orexin inhibits the expression of proinflammatory cytokines. Ghrelin leads to a dose-dependent inhibition of leptin-induced cytokines and leptin itself increases ghrelin receptors on T lymphocytes [165]. This hormonal/immune network between ghrelin and leptin contributes to regulate the balance between effector and tolerant immune response and involves also calcitriol as an effector hormone. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Vitamin D and its active form 1α,25(OH)2D3 has been recently indicated to have a fundamental role in immune regulation. An interplay between gut and white adipose tissue (WAT), mainly mediated by enterogastric hormones and adipokines, such as leptin, adiponectin and ghrelin, actively participate in the immune homeostasis and modulation both of the innate/acquired immune response and between T-cell effector/T-cell regulatory skewing. Particularly for leptin, this action promotes and enhances immune tolerance at the gut level and pro-inflammatory effect at WAT level, while calcitriol participates in promoting and increasing an M2 macrophage-like skewing, a T-reg activity at WAT level and a iNKT function at gut level. The role of active vitamin D3 therefore is fundamental in the immune homeostasis of the WAT immune microenvironment and to support the role of WAT as an endocrine, tolerogenic organ.
    Full-text · Article · Jul 2015
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    • "Furthermore, the expression of ApN receptor (coupled with the co-stimulatory molecule CTLA-4) is up-regulated on activated T cell surface and associated with enhanced apoptosis and suppressed cytokine production [207]. On the other hand, ghrelin suppressed Th1, Th2 and Th17 phenotypes in both physiological T cell development [208] [209] [210] and inflammatory conditions [186] [211]. "
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