Decreased severity of experimental autoimmune encephalomyelitis during resveratrol administration is associated with increased IL-17⁺IL-10⁺ T cells, CD4^- IFN-γ⁺ 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-γ, TNF-α, 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-γ 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-γ, and TNF-α. 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-γ ⁺ 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-γ⁺ and with repressed macrophage IL-6 and IL-12/23 p40 expression.