Decline in intestinal mucosal IL-10 expression and decreased intestinal barrier function in a mouse model of total parenteral nutrition

Abstract

Loss of intestinal epithelial barrier function (EBF) is a major problem associated with total parenteral nutrition (TPN) administration. We have previously identified intestinal intraepithelial lymphocyte (IEL)-derived interferon-gamma (IFN-gamma) as a contributing factor to this barrier loss. The objective was to determine whether other IEL-derived cytokines may also contribute to intestinal epithelial barrier breakdown. C57BL6J male mice received TPN or enteral nutrition (control) for 7 days. IEL-derived interleukin-10 (IL-10) was then measured. A significant decline in IEL-derived IL-10 expression was seen with TPN administration, a cytokine that has been shown in vitro to maintain tight junction integrity. We hypothesized that this change in IEL-derived IL-10 expression could contribute to TPN-associated barrier loss. An additional group of mice was given exogenous recombinant IL-10. Ussing chamber experiments showed that EBF markedly declined in the TPN group. TPN resulted in a significant decrease of IEL-derived IL-10 expression. The expression of several tight junction molecules also decreased with TPN administration. Exogenous IL-10 administration in TPN mice significantly attenuated the TPN-associated decline in zonula occludens (ZO)-1, E-cadherin, and occludin expression, as well as a loss of intestinal barrier function. TPN administration led to a marked decline in IEL-derived IL-10 expression. This decline was coincident with a loss of intestinal EBF. As the decline was partially attenuated with the administration of exogenous IL-10, our findings suggest that loss of IL-10 may be a contributing mechanism to TPN-associated epithelial barrier loss.

Cysteinyl-glycine reduces mucosal proinflammatory cytokine response to fMLP in a parenterally-fed piglet model

“…Piglets receiving PN, however, had lower mucosal IL-10 compared to their sow-fed littermates. Parenteral nutrition has been documented to lower IL-10 concentration (28,29), and to increase intestinal permeability (30-32); however, no difference in ileal permeability was detected in this study. As IL-10 can suppress IFN-γ production (33), the lower IL-10 concentrations in PN-fed animals could have contributed to the higher concentrations of IFN-γ found in this piglets when compared to SF littermates.…”

Homeostasis alteration within small intestinal mucosa after acute enteral refeeding in total parenteral nutrition mouse model

“…T regulator cell-produced cytokines IL-10 and TGF-␤ are known to modulate the proinflammatory response with TPN (20) and can sustain IEC proliferation and apoptosis (41). In our TPN model, it had been reported that TPN administration decreased IL-10 and TGF-␤ expression.…”

Dietary tryptophan modulates intestinal immune response, barrier function, antioxidant status and gene expression of TOR and Nrf2 in young grass carp (Ctenopharyngodon idella)

“…Several lines of evidence support a barrier-forming role for ZO-1, occludin, claudin-b, -c and -3 in fish [77,78], whereas claudin-12 and -15 in rats seem to possess pore-forming characteristics [79,80]. Moreover, the up-regulation of ZO-1 and occludin [81] and down-regulation of claudin-15 [82] attenuated the loss of the Fig. 8.…”

“…Another study showed that TNF-a could down-regulate the expression of occludin in human intestinal epithelial cells, leading to damage in the mucosal barrier [84]. Conversely, exogenous IL-10 administration up-regulated the gene expression levels of ZO-1 and occludin in rat intestinal epithelial cells [81]. As presented above, dietary Trp down-regulated the mRNA levels of TNF-a and up-regulated the IL-10 gene expression in all intestinal segments of young grass carp.…”