Sickness behavior induced by endotoxin can be mitigated by the dietary soluble fiber, pectin, through up-regulation of IL-4 and Th2 polarization.
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-1beta and TNF-alpha 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-gamma when compared to mice fed insoluble fiber. Likewise, endotoxin-stimulated macrophages from mice fed soluble fiber demonstrated decreased IL-1beta, TNF-alpha, IFN-gamma, 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.
Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USA.
Christina L
CL
Sherry
Stephanie S
SS
Kim
Ryan N
RN
Dilger
Laura L
LL
Bauer
Morgan L
ML
Moon
Richard I
RI
Tapping
George C
GC
Fahey
Kelly A
KA
Tappenden
Gregory G
GG
Freund
D000818:Animals; D000930:Antidiarrheals / Q000494:pharmacology; D016207:Cytokines / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004035:Diet Therapy / Q000379:methods*; D004043:Dietary Fiber / Q000145:classification / Q000494:pharmacology*; D004731:Endotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D007082:Ileum / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D055809:Illness Behavior; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D015847:Interleukin-4 / Q000172:deficiency / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics; D010368:Pectins / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000294:innervation; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
D000930:Antidiarrheals; D016207:Cytokines; D004043:Dietary Fiber; D004731:Endotoxins; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D007376:Interleukin-2; D015850:Interleukin-6; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma; D010368:Pectins