Decreased severity of experimental autoimmune encephalomyelitis during resveratrol administration is associated with increased IL-17+IL-10+ T cells, CD4(-) IFN-gamma+ cells, and decreased macrophage IL-6 expression

Int Immunopharmacol. 2009 Jan;9(1):134-43. doi: 10.1016/j.intimp.2008.10.015. Epub 2008 Nov 18.


Experimental autoimmune encephalomyelitis (EAE), an animal model of Multiple Sclerosis, is induced after injection of PLP(139-151) myelin peptide in complete Freund's adjuvant into SJL/J mice. During EAE, T cells and macrophages infiltrate the brain, produce cytokines IL-17, IFN-gamma, TNF-alpha, or IL-6, and bring about autoimmune neuroinflammation. However, infiltrating T cells which simultaneously produce IL-17 and IL-10 or infiltrating CD4(-) NKT cells that produce IFN-gamma protect against EAE. Resveratrol, a plant polyphenol, exhibits anti-inflammatory properties. To determine if resveratrol can relieve EAE, SJL/J mice were administered diets enriched in resveratrol at EAE injection. EAE symptoms were significantly less compared with controls in mice fed resveratrol. At day 56 of EAE, splenic T cells from mice fed 0%, 0.04% or 0.08% resveratrol that were restimulated with PLP(139-151) produced similar levels while splenic T cells from mice fed 0.02% resveratrol produced significantly higher levels of IL-17, IFN-gamma, and TNF-alpha. At peak EAE (day 14), mice fed resveratrol had higher numbers of IL-17+ T cells, IL-17+/IL-10+ T cells, and CD4(-)IFN-gamma+ cells in the brain and spleen compared with controls. Adoptive transfer of day 14 EAE encephalogenic T cells into mice fed resveratrol reduced the severity of EAE. In addition, resveratrol directly suppressed expression of IL-6 and IL-12/23 p40 but increased expression of IL-12 p35 and IL-23 p19 from macrophages. Therefore resveratrol protection against EAE is not associated with declines in IL-17+ T cells but is associated with rises in IL-17+/IL-10+ T cells and CD4(-)IFN-gamma+ and with repressed macrophage IL-6 and IL-12/23 p40 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Brain / cytology
  • CD4 Antigens / biosynthesis*
  • Diet
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Female
  • Flow Cytometry
  • Freund's Adjuvant
  • Immunotherapy, Adoptive
  • Interferon-gamma / biosynthesis*
  • Interleukin-10 / biosynthesis*
  • Interleukin-17 / biosynthesis*
  • Interleukin-6 / biosynthesis*
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • Monocytes / drug effects
  • Monocytes / immunology
  • Myelin Proteolipid Protein / pharmacology
  • Peptide Fragments / pharmacology
  • Resveratrol
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen / cytology
  • Spleen / drug effects
  • Spleen / immunology
  • Stilbenes / pharmacology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / metabolism*


  • Anti-Inflammatory Agents, Non-Steroidal
  • CD4 Antigens
  • Interleukin-17
  • Interleukin-6
  • Myelin Proteolipid Protein
  • Peptide Fragments
  • Stilbenes
  • myelin proteolipid protein (139-151)
  • Interleukin-10
  • Interferon-gamma
  • Freund's Adjuvant
  • Resveratrol