Sickness behavior induced by endotoxin can be mitigated by the dietary soluble fiber, pectin, through up-regulation of IL-4 and Th2 polarization
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- 作者：Christina L. Sherry ; Stephanie S. Kim ; Ryan N. Dilger ; Laura L. Bauer ; Morgan L. Moon ; Richard I. Tapping ; George C. Fahey Jr. ; Kelly A. Tappenden ; Gregory G. Freund
- 关键词：Sickness behavior ; Cytokines ; Dietary fiber ; Th1/Th2 ; IL-4 ; Macrophage alternative activation
- 刊名：Brain, Behavior, and Immunity
- 出版年：2010
- 出版时间：May 2010
- 年：2010
- 卷：24
- 期：4
- 页码：631-640
- 全文大小：408 K
文摘
Peripheral activation of the immune system by infectious agents triggers the brain–cytokine system causing sickness behaviors which profoundly impact well-being. Dietary fiber is a beneficial foodstuff that, from a gastrointestinal tract perspective, exists in both insoluble and soluble forms. We show that a diet rich in soluble fiber protects mice from endotoxin-induced sickness behavior by polarizing mice Th2 when compared to a diet containing only insoluble fiber. Mice fed soluble fiber became less sick and recovered faster from endotoxin-induced sickness behaviors than mice fed insoluble fiber. In response to intraperitoneal endotoxin, mice fed soluble fiber had up-regulated IL-1RA and reduced IL-1β and TNF-α in the brain as compared to mice fed insoluble fiber. Importantly, mice fed soluble fiber had a basal increase in IL-4 in the ileum and spleen which was absent in MyD88 knockout mice. Con-A stimulated splenocytes from mice fed soluble fiber showed increased IL-4 and IL-5 and decreased IL-2, IL-12 and IFN-γ when compared to mice fed insoluble fiber. Likewise, endotoxin-stimulated macrophages from mice fed soluble fiber demonstrated decreased IL-1β, TNF-α, IFN-γ, IL-12 and nitrate and increased IL-1RA, arginase 1 and Ym1 when compared to mice fed insoluble fiber. Finally, the behavioral protection afforded by feeding mice soluble fiber was reduced in IL-4 knockout mice, as was the impact of soluble fiber on Con-A stimulated splenocytes and endotoxin activated macrophages. These data show that a diet rich in soluble fiber protects against endotoxin-induced sickness behavior by polarizing mice Th2 and promoting alternative activation of macrophages.