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

作者：Imler Toby J Jr; Petro Thomas M^*

来源：International Immunopharmacology, 2009, 9(1): 134-143.

DOI：10.1016/j.intimp.2008.10.015

• Resveratrol
• EAE
• Cytokines
• Macrophages
• T cells

Experimental autoimmune encephalomyelitis (EAE), an animal model of Multiple Sclerosis, is induced after injection of PLP139-151 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 PLP139-151 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 resverattol 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 p-19 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.

• 出版日期2009-1