Ghrelin Suppression of Autoimmune Encephalomyelitis

Abstract

Ghrelin is a gastric hormone first identified in the rat stomach as a mediator of growth hormone (GH) release. The biological effect of ghrelin is mediated by a G protein-coupled receptor called GH secretagogue receptor (GHS-R). Although ghrelin is predominantly secreted from mucosal endocrine cells of the stomach, ghrelin and GHS-R are widely distributed throughout various organs including immune cells and lymphoid tissues. Ghrelin induces increases in peripheral blood lymphocyte numbers as well as increases in thymic cellularity and differentiation, thus augmenting cytotoxic lymphocytes and reducing tumor initiation and subsequent metastases. More recent studies have highlighted the anti-inflammatory functions of ghrelin. For example, we have demonstrated that exogenous ghrelin influences the development of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis. In the C57BL/6 mouse model of EAE in which disease is induced by sensitization to myelin oligodendrocyte glycoprotein 35–55 peptide, we found that injections of ghrelin significantly reduced the clinical severity of EAE. The suppression of EAE was accompanied by a reduction in the mRNA levels of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6 in the spinal cord cellular infiltrates and microglia from ghrelin-treated mice at the peak of disease, suggesting that ghrelin may act as an anti-inflammatory hormone. Consistent with these findings, ghrelin significantly suppressed the production of proinflammatory cytokines in LPS-stimulated microglia in vitro. These results shed light on a new role for ghrelin in the regulation of inflammation with possible implications for the management of human diseases.