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* Department of Immunology, National Institute of Neuroscience, National Centre of Neurology and Psychiatry, Tokyo, Japan;
Department of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany:
Department of Biochemistry, National Cardiovascular Center Research Institute, Fujishirodai, Suita, Osaka, Japan;
Experimental Therapy, Franz-Penzoldt-Center, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; and
¶ Ghrelin Research Project, Translational Research Center, Kyoto University Faculty of Medicine, Kyoto, Japan
Ghrelin is a recently identified gastric hormone that displays strong growth hormone-releasing activity mediated by the growth hormone secretagogue receptor. While this unique endogenous peptide participates in the regulation of energy homeostasis, increases food intake, and decreases energy expenditure, its ability to inhibit the production of proinflammatory cytokines in vitro indicates its role in the regulation of inflammatory process in vivo. Here we examine the effect of exogenous ghrelin on the development of experimental autoimmune encephalomyelitis (EAE), a representative model of multiple sclerosis. In the C57BL/6 mouse model of EAE induced by sensitization to myelin oligodendrocyte glycoprotein 35–55 peptide, we found that alternate-day s.c. injections of ghrelin (5 µg/kg/day) from day 1 to 35 significantly reduced the clinical severity of EAE. The suppression of EAE was accompanied by reduced mRNA levels of proinflammatory cytokines such as TNF-
, IL-1β, and IL-6 in the spinal cord cellular infiltrates and microglia from ghrelin-treated mice at the peak of disease, suggesting the role of ghrelin as an antiinflammatory hormone. Consistently, ghrelin significantly suppressed the production of proinflammatory cytokines in LPS-stimulated microglia in vitro. These results shed light on the new role of ghrelin in the regulation of inflammation with possible implications for management of human diseases.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the grants from the Ministry of Health, Labor, and Welfare of Japan, the Program for Promotion of Fundamental Studies in Health Sciences of the National Institute of Biomedical Innovation (NIBIO), and the Ministry of Education, Science, Culture, Sports, and Technology of Japan.
2 Address correspondence and reprint requests to Dr. Sachiko Miyake or Dr. Takashi Yamamura, Department of Immunology, National Institute of Neuroscience, National Centre of Neurology and Psychiatry, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187-8502. E-mail address: miyake{at}ncnp.go.jp or yamamura{at}ncnp.go.jp
3 Abbreviations used in this paper: GH, growth hormone; EAE, experimental autoimmune encephalomyelitis; GHS, growth hormone secretagogue; GHS-R, growth hormone secretagogue receptor; LN, lymph node; MOG, myelin oligodendrocyte glycoprotein; NPY, neuropeptide Y.
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