Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells.
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.
Dixit
Vishwa Deep
VD
Laboratory of Immunology, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA.
Schaffer
Eric M
EM
Pyle
Robert S
RS
Collins
Gary D
GD
Sakthivel
Senthil K
SK
Palaniappan
Ravichandran
R
Lillard
James W
JW
Taub
Dennis D
DD
D016207:Cytokines / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D054439:Ghrelin; D019382:Human Growth Hormone / Q000494:pharmacology; D006801:Humans; D007249:Inflammation; D020738:Leptin / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D009000:Monocytes / Q000187:drug effects / Q000276:immunology*; D036361:Peptide Hormones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D054440:Receptors, Ghrelin; D054411:Receptors, Leptin; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*
D016207:Cytokines; D054439:Ghrelin; C515448:LEPR protein, human; D020738:Leptin; D036361:Peptide Hormones; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D054440:Receptors, Ghrelin; D054411:Receptors, Leptin; D019382:Human Growth Hormone