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PMID: 15232612 Published · ppublish English Journal Article

Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells.

The Journal of clinical investigation ·Vol. 114 ·No. 1 ·2004-07-00 ·Pages 57-66

Dixit VD, Schaffer EM, Pyle RS, Collins GD, Sakthivel SK, Palaniappan R, Lillard JW, Taub DD

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.

MeSH Terms
Cytokines/genetics Dose-Response Relationship, Drug Gene Expression Regulation/drug effects,immunology Ghrelin Human Growth Hormone/pharmacology Humans Inflammation Leptin/antagonists & inhibitors,pharmacology Lymphocyte Activation/drug effects Monocytes/drug effects,immunology Peptide Hormones/pharmacology RNA, Messenger/genetics Receptors, G-Protein-Coupled/genetics,immunology,physiology Receptors, Ghrelin Receptors, Leptin T-Lymphocytes/drug effects,immunology
Chemicals
Cytokines Ghrelin Leptin Peptide Hormones RNA, Messenger Receptors, G-Protein-Coupled Receptors, Ghrelin Receptors, Leptin leptin receptor, human Human Growth Hormone
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Dixit Vishwa Deep
Laboratory of Immunology, National Institute on Aging, NIH, Baltimore, Maryland 21224, USA.
Schaffer Eric M
Pyle Robert S
Collins Gary D
Sakthivel Senthil K
Palaniappan Ravichandran
Lillard James W
Taub Dennis D
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI21134
Published
2004-07-00
Pages
57-66
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC437970
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI21134 PMC Full Text View journal details
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