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. 2006 May;144(2):273-80.
doi: 10.1111/j.1365-2249.2006.03051.x.

Role of Interleukin (IL-10) in Probiotic-Mediated Immune Modulation: An Assessment in Wild-Type and IL-10 Knock-Out Mice

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Free PMC article

Role of Interleukin (IL-10) in Probiotic-Mediated Immune Modulation: An Assessment in Wild-Type and IL-10 Knock-Out Mice

B Sheil et al. Clin Exp Immunol. .
Free PMC article

Abstract

While the impact of Bifidobacterium infantis 35624 and other probiotics on cytokines has been shown in established colitis, the effects of B. infantis consumption in pre-inflammation of interleukin (IL)-10 knock-out (KO) mice and on the wild-type (WT) C57Bl/6 mice have not been well demonstrated. The objective of this study was to examine cytokine responses in mucosal and systemic lymphoid compartments of IL-10 KO mice early in disease and to compare with control WT mice. Mice were fed B. infantis or placebo for 5 weeks and culled prior to the onset of chronic intestinal inflammation (12-14 weeks). The spleen, Peyer's patches and intestinal mucosa were removed and stimulated with various bacterial stimuli. Cytokine levels were measured by enzyme-linked immunosorbent assay. While basal intestinal and systemic cytokine profiles of WT and IL-10 KO mice were similar, transforming growth factor (TGF)-beta was reduced in the spleen of IL-10 KO mice. Following probiotic consumption, interferon (IFN)-gamma was reduced in the Peyer's patch of both WT and IL-10 KO mice. Alterations in IFN-gamma in the Peyer's patches of WT mice (enhancement) versus IL-10 KO (reduction) were observed following in vitro stimulation with salmonella. Differential IL-12p40, CCL2 and CCL5 responses were also observed in IL-10 KO mice and WT mice. The cytokine profile of IL-10 KO mice in early disease was similar to that of WT mice. The most pronounced changes occurred in the Peyer's patch of IL-10 KO mice, suggesting a probiotic mechanism of action independent of IL-10. This study provides a rationale for the use of B. infantis 35624 for the treatment of gastrointestinal inflammation.

Figures

Fig. 1
Fig. 1
Confirmation of early disease in interleukin (IL)-10 knock-out (KO) mice. IL-10 KO mice were investigated over 43 weeks and scores for disease activity and histology taken. At 12–14 weeks mice had a disease activity index of 1 (a) and a low histology score (b), indicating minimal inflammation at this time.
Fig. 2
Fig. 2
Spontaneous cytokine production by supernatants of cells isolated from the Peyer's patch, gut mucosa and spleens of wild-type (WT) and interleukin (IL)-10 knock-out (KO) mice. The level of (a) IL-12p40 was decreased significantly in the Peyer's patch, (b) CCL5 increased significantly in the gut mucosa and (c) transforming growth factor (TGF)-β1 attenuated significantly in the spleen of IL-10 KO compared to WT mice. *P< 0·05. Results expressed as mean ± standard error, n = 8–12 mice.
Fig. 3
Fig. 3
Cytokine production by supernatants of cells isolated from the Peyer's patch of (a) wild-type (WT) and (b) interleukin (IL)-10 knock-out (KO) mice following Bifidobacterium infantis 35624 and placebo feeding. Interferon (IFN)-γ was attenuated significantly in WT and IL-10 KO mice following probiotic consumption. IL-4 was reduced significantly in WT mice only and tumour necrosis factor (TNF)-α was reduced significantly in IL-10 KO mice only. *P< 0·05. Results expressed as mean ± standard error, n = 8–12 mice.
Fig. 4
Fig. 4
Change in cytokine production from Peyer's patch cells isolated from of wild-type (WT) and interleukin (IL)-10 knock-out (KO) mice fed Bifidobacterium infantis 35624 following in vitro stimulation with bacterial stimuli. The levels of (a) interferon (IFN)-γ, (b) IL-12p40, (c) CCL5 and (d) CCL2 production by Peyer's patch cells of WT and IL-10 KO mice following placebo and B. infantis 35624 feeding and in vitro challenge with bacterial stimuli. IFN-γ was attenuated significantly in all mice following probiotic consumption. However, a striking difference between IL-10 KO and WT mice following probiotic consumption and in vitro stimulation was noted, particularly with Salmonella typhimurium UK1 challenge, where IFN-γ was attenuated significantly in IL-10 KO mice but enhanced significantly in WT. IL-12p40 and CCL5 levels were enhanced significantly in IL-10 KO mice following probiotic feeding. CCL2 was decreased significantly in IL-10 KO mice fed B. infantis 35624 following in vitro challenge. In contrast, there was no significant change in IL-12p40, CCL5 and CCL2 levels in WT mice following B. infantis 35624 consumption. Results are expressed as percentage change [(B. infantis 35624 fed − control fed/control fed) × 100] for WT and IL-10 KO mice. *P< 0·05, n = 8–12 mice. Statistical comparison of control-fed versus probiotic-fed in WT and IL-10 KO mice.

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