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.
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.
Imler
Toby J
TJ
Dept. of Oral Biology, University of Nebraska Medical Center, Lincoln, Nebraska 68583, USA.
Petro
Thomas M
TM
D019264:Adoptive Transfer; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001921:Brain / Q000166:cytology; D015704:CD4 Antigens / Q000096:biosynthesis*; D004032:Diet; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D005620:Freund's Adjuvant; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000096:biosynthesis*; D016753:Interleukin-10 / Q000096:biosynthesis*; D020381:Interleukin-17 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000096:biosynthesis*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D018991:Myelin Proteolipid Protein / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013267:Stilbenes / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015704:CD4 Antigens; D020381:Interleukin-17; D015850:Interleukin-6; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D013267:Stilbenes; C435023:myelin proteolipid protein (139-151); D016753:Interleukin-10; D007371:Interferon-gamma; D005620:Freund's Adjuvant; D000077185:Resveratrol