Sickness behavior induced by endotoxin can be mitigated by the dietary soluble fiber, pectin, through up-regulation of IL-4 and Th2 polarization - PubMed (original) (raw)

Comparative Study

Sickness behavior induced by endotoxin can be mitigated by the dietary soluble fiber, pectin, through up-regulation of IL-4 and Th2 polarization

Christina L Sherry et al. Brain Behav Immun. 2010 May.

Abstract

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.

Copyright 2010 Elsevier Inc. All rights reserved.

PubMed Disclaimer

Figures

Fig. 1

Fig. 1. Soluble fiber protects against endotoxemia

A, Chow and 5% cellulose (cellulose) fed mice were administered carrier (PBS) or LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS. B, 10% pectin (pectin) and cellulose fed mice were administered LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS. C, Pectin and cellulose fed mice were administered LPS IP (0 h) and temperature measured. Results are expressed as a change from pre-LPS (0 h) measurement, means ± SEM; n = 4; arrowp<0.05, main effect of time. D, Pectin and cellulose fed mice were administered LPS IP and food intake and body weight measured 24 h post LPS. Results are expressed as percentage change from the pre-LPS measurement, means ± SEM; n = 4; *p<0.05, main effect of diet. E, Pectin and 10% cellulose fed mice were administered LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS

Fig. 1

Fig. 1. Soluble fiber protects against endotoxemia

A, Chow and 5% cellulose (cellulose) fed mice were administered carrier (PBS) or LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS. B, 10% pectin (pectin) and cellulose fed mice were administered LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS. C, Pectin and cellulose fed mice were administered LPS IP (0 h) and temperature measured. Results are expressed as a change from pre-LPS (0 h) measurement, means ± SEM; n = 4; arrowp<0.05, main effect of time. D, Pectin and cellulose fed mice were administered LPS IP and food intake and body weight measured 24 h post LPS. Results are expressed as percentage change from the pre-LPS measurement, means ± SEM; n = 4; *p<0.05, main effect of diet. E, Pectin and 10% cellulose fed mice were administered LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS

Fig. 1

Fig. 1. Soluble fiber protects against endotoxemia

A, Chow and 5% cellulose (cellulose) fed mice were administered carrier (PBS) or LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS. B, 10% pectin (pectin) and cellulose fed mice were administered LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS. C, Pectin and cellulose fed mice were administered LPS IP (0 h) and temperature measured. Results are expressed as a change from pre-LPS (0 h) measurement, means ± SEM; n = 4; arrowp<0.05, main effect of time. D, Pectin and cellulose fed mice were administered LPS IP and food intake and body weight measured 24 h post LPS. Results are expressed as percentage change from the pre-LPS measurement, means ± SEM; n = 4; *p<0.05, main effect of diet. E, Pectin and 10% cellulose fed mice were administered LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS

Fig. 1

Fig. 1. Soluble fiber protects against endotoxemia

A, Chow and 5% cellulose (cellulose) fed mice were administered carrier (PBS) or LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS. B, 10% pectin (pectin) and cellulose fed mice were administered LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS. C, Pectin and cellulose fed mice were administered LPS IP (0 h) and temperature measured. Results are expressed as a change from pre-LPS (0 h) measurement, means ± SEM; n = 4; arrowp<0.05, main effect of time. D, Pectin and cellulose fed mice were administered LPS IP and food intake and body weight measured 24 h post LPS. Results are expressed as percentage change from the pre-LPS measurement, means ± SEM; n = 4; *p<0.05, main effect of diet. E, Pectin and 10% cellulose fed mice were administered LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS

Fig. 1

Fig. 1. Soluble fiber protects against endotoxemia

A, Chow and 5% cellulose (cellulose) fed mice were administered carrier (PBS) or LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS. B, 10% pectin (pectin) and cellulose fed mice were administered LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS. C, Pectin and cellulose fed mice were administered LPS IP (0 h) and temperature measured. Results are expressed as a change from pre-LPS (0 h) measurement, means ± SEM; n = 4; arrowp<0.05, main effect of time. D, Pectin and cellulose fed mice were administered LPS IP and food intake and body weight measured 24 h post LPS. Results are expressed as percentage change from the pre-LPS measurement, means ± SEM; n = 4; *p<0.05, main effect of diet. E, Pectin and 10% cellulose fed mice were administered LPS IP and social withdrawal measured prior to LPS (0 h) and at 2, 4, 8 and 12 h post LPS. Results are expressed as percentage change from the 0 h measurement, means ± SEM; n = 8; *p<0.05, main effect of diet, #p<0.05, treatment effect of LPS

Fig. 2

Fig. 2. Soluble fiber up-regulates IL-1RA

10% pectin (pectin) and 5% cellulose (cellulose) fed mice were administered carrier (PBS) or LPS IP. At 2 h post LPS, real-time RT-PCR was used to quantify IL-1RA (A), IL-1β(B), TNF-α(B) and IL-6 (B) mRNAs from brain. Results are expressed as relative change in mRNA expression ( mRNA), means ± SEM; n = 6-8; *p<0.05 main effect of diet, #p<0.05 treatment effect of LPS.

Fig. 2

Fig. 2. Soluble fiber up-regulates IL-1RA

10% pectin (pectin) and 5% cellulose (cellulose) fed mice were administered carrier (PBS) or LPS IP. At 2 h post LPS, real-time RT-PCR was used to quantify IL-1RA (A), IL-1β(B), TNF-α(B) and IL-6 (B) mRNAs from brain. Results are expressed as relative change in mRNA expression ( mRNA), means ± SEM; n = 6-8; *p<0.05 main effect of diet, #p<0.05 treatment effect of LPS.

Fig. 3

Fig. 3. IL-4 production is augmented by soluble fiber

Mice were fed 10% pectin (pectin) or 5% cellulose (cellulose) for 6 wks. A, Real-time RT-PCR was used to quantify IL-4 mRNAs from the indicated tissues. Results are expressed as relative change in mRNA expression (ΔmRNA), means ± SEM; n = 6-8; *p<0.05 main effect of diet. B, ELISA was used to quantify IL-4 from the indicated tissues. Results are expressed as means ± SEM; n = 5-7; *p<0.05 main effect of diet. C, Wild type (WT) and MyD88 KO mice were fed 10% pectin (pectin) or 5% cellulose (cellulose) for 6 wks. Real-time RT-PCR was used to quantify IL-4 mRNAs from the indicated tissues. Results are expressed as relative change in mRNA expression (ΔmRNA), means ± SEM; n = 3; *p<0.05 main effect of diet.

Fig. 3

Fig. 3. IL-4 production is augmented by soluble fiber

Mice were fed 10% pectin (pectin) or 5% cellulose (cellulose) for 6 wks. A, Real-time RT-PCR was used to quantify IL-4 mRNAs from the indicated tissues. Results are expressed as relative change in mRNA expression (ΔmRNA), means ± SEM; n = 6-8; *p<0.05 main effect of diet. B, ELISA was used to quantify IL-4 from the indicated tissues. Results are expressed as means ± SEM; n = 5-7; *p<0.05 main effect of diet. C, Wild type (WT) and MyD88 KO mice were fed 10% pectin (pectin) or 5% cellulose (cellulose) for 6 wks. Real-time RT-PCR was used to quantify IL-4 mRNAs from the indicated tissues. Results are expressed as relative change in mRNA expression (ΔmRNA), means ± SEM; n = 3; *p<0.05 main effect of diet.

Fig. 3

Fig. 3. IL-4 production is augmented by soluble fiber

Mice were fed 10% pectin (pectin) or 5% cellulose (cellulose) for 6 wks. A, Real-time RT-PCR was used to quantify IL-4 mRNAs from the indicated tissues. Results are expressed as relative change in mRNA expression (ΔmRNA), means ± SEM; n = 6-8; *p<0.05 main effect of diet. B, ELISA was used to quantify IL-4 from the indicated tissues. Results are expressed as means ± SEM; n = 5-7; *p<0.05 main effect of diet. C, Wild type (WT) and MyD88 KO mice were fed 10% pectin (pectin) or 5% cellulose (cellulose) for 6 wks. Real-time RT-PCR was used to quantify IL-4 mRNAs from the indicated tissues. Results are expressed as relative change in mRNA expression (ΔmRNA), means ± SEM; n = 3; *p<0.05 main effect of diet.

Fig. 4

Fig. 4. Arginase and Ym1 expression in peritoneal macrophages

Mice were fed 10% pectin (pectin) or 5% cellulose (cellulose) for 6 wks. Real-time RT-PCR was used to quantify arginase (Arg) and Ym1 mRNAs from peritoneal macrophages. Results are expressed as relative change in mRNA expression (ΔmRNA), means ± SEM; n = 6-8; *p<0.05 main effect of diet.

Fig. 5

Fig. 5. IL-4 knockout (KO) blunts the impact of soluble fiber on endotoxemia resistance

A, 10% pectin (pectin) and 5% cellulose (cellulose) fed wild type (WT) and IL-4 KO mice were administered carrier (PBS) or LPS IP and social withdrawal measured at 2 h post LPS. Results are expressed as percentage change from cellulose PBS WT mice, means ± SEM; n = 3-4; #p<0.05, treatment effect of LPS, *p<0.05 main effect of diet, $p<0.05 phenotype effect. B, IL-4 KO mice were fed 10% pectin (pectin) or 5% cellulose (cellulose) for 6 wks. Real-time RT-PCR was used to quantify arginase (Arg) and Ym1 mRNAs from peritoneal macrophages. Results are expressed as relative change in mRNA expression (ΔmRNA), means ± SEM; n = 3; *p<0.05 main effect of diet.

Fig. 5

Fig. 5. IL-4 knockout (KO) blunts the impact of soluble fiber on endotoxemia resistance

A, 10% pectin (pectin) and 5% cellulose (cellulose) fed wild type (WT) and IL-4 KO mice were administered carrier (PBS) or LPS IP and social withdrawal measured at 2 h post LPS. Results are expressed as percentage change from cellulose PBS WT mice, means ± SEM; n = 3-4; #p<0.05, treatment effect of LPS, *p<0.05 main effect of diet, $p<0.05 phenotype effect. B, IL-4 KO mice were fed 10% pectin (pectin) or 5% cellulose (cellulose) for 6 wks. Real-time RT-PCR was used to quantify arginase (Arg) and Ym1 mRNAs from peritoneal macrophages. Results are expressed as relative change in mRNA expression (ΔmRNA), means ± SEM; n = 3; *p<0.05 main effect of diet.

Similar articles

Cited by

References

    1. Ansel KM, Djuretic I, Tanasa B, Rao A. Regulation of Th2 differentiation and Il4 locus accessibility. Annu Rev Immunol. 2006;24:607–656. - PubMed
    1. Arend WP, Palmer G, Gabay C. IL-1, IL-18, and IL-33 families of cytokines. Immunol Rev. 2008;223:20–38. - PubMed
    1. Bowen H, Kelly A, Lee T, Lavender P. Control of cytokine gene transcription in Th1 and Th2 cells. Clin Exp Allergy. 2008;38:1422–1431. - PubMed
    1. Burgess W, Gheusi G, Yao J, Johnson RW, Dantzer R, Kelley KW. Interleukin-1beta-converting enzyme-deficient mice resist central but not systemic endotoxin-induced anorexia. Am J Physiol. 1998;274:R1829–33. - PubMed
    1. Cavaglieri CR, Nishiyama A, Fernandes LC, Curi R, Miles EA, Calder PC. Differential effects of short-chain fatty acids on proliferation and production of pro- and anti-inflammatory cytokines by cultured lymphocytes. Life Sci. 2003;73:1683–1690. - PubMed

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources