Therapeutic effect of ghrelin in experimental autoimmune encephalomyelitis by inhibiting antigen-specific Th1/Th17 responses and inducing regulatory T cells

Brain Behav Immun. 2013 May:30:54-60. doi: 10.1016/j.bbi.2013.01.080. Epub 2013 Jan 29.

Abstract

Ghrelin is an important gastrointestinal hormone that regulates feeding and metabolism. Moreover, ghrelin is produced by immune cells and shows potent anti-inflammatory activities. Here, we investigated its effect in two models of experimental autoimmune encephalomyelitis (EAE) that mirror chronic and relapsing-remitting multiple sclerosis. A short systemic treatment with ghrelin after the disease onset reduced clinical severity and incidence of both forms of EAE, which was associated with a decrease in inflammatory infiltrates in spinal cord and in the subsequent demyelination. This therapeutic effect was exerted through the reduction of the autoimmune and inflammatory components of the disease. Ghrelin decreased the presence/activation of encephalitogenic Th1 and Th17 cells in periphery and nervous system, down-regulated various inflammatory mediators, and induced regulatory T cells. In summary, our findings provide a powerful rationale for the assessment of the efficacy of ghrelin as a novel therapeutic approach for treating multiple sclerosis through distinct immunomodulatory mechanisms and further support the concept that the neuroendocrine and immune systems crosstalk to finely tune the final immune response of our body.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cytokines / metabolism
  • Down-Regulation / drug effects
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Forkhead Transcription Factors / metabolism
  • Ghrelin / pharmacology
  • Ghrelin / therapeutic use*
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Inflammation / metabolism
  • Mice
  • Spinal Cord / drug effects
  • Spinal Cord / immunology
  • Spinal Cord / metabolism
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / drug effects*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology
  • Th17 Cells / metabolism

Substances

  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Ghrelin