Suppression of experimental autoimmune encephalomyelitis by ghrelin.
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 mug/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-alpha, IL-1beta, 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.
Theil
Michael-Mark
MM
Department of Immunology, National Institute of Neuroscience, National Centre of Neurology and Psychiatry, Tokyo, Japan.
Miyake
Sachiko
S
Mizuno
Miho
M
Tomi
Chiharu
C
Croxford
J Ludovic
JL
Hosoda
Hiroshi
H
Theil
Julia
J
von Hörsten
Stephan
S
Yokote
Hiroaki
H
Chiba
Asako
A
Lin
Youwei
Y
Oki
Shinji
S
Akamizu
Takashi
T
Kangawa
Kenji
K
Yamamura
Takashi
T
D000595:Amino Acid Sequence; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage*; D002460:Cell Line; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D005260:Female; D054439:Ghrelin / Q000008:administration & dosage*; D006801:Humans; D018836:Inflammation Mediators / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000037:antagonists & inhibitors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics; D000093242:Interleukin-6 Inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D054439:Ghrelin; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C422650:ghrelin, des-n-octanoyl