Moderate zinc restriction affects intestinal health and immune function in lipopolysaccharide-challenged mice

Abstract

Zinc (Zn) is an essential nutrient that affects immune function, especially within the digestive system, although the underlying mechanisms are not well understood. This study examined the effects of short-term moderate Zn restriction on intestinal health and immune function in lipopolysaccharide (LPS)-challenged mice through plasma cytokine profiling and histological evaluation of intestinal tissue sections. Adult male mice were fed with a Zn-adequate (40 ppm) or a Zn-marginal (4 ppm) diet for 4 weeks, and then a bacterial challenge was simulated by intraperitoneal injection of LPS (10 μg/g body weight [BW]) or saline (control). BW was recorded weekly, and feed intake was recorded daily over the last week. Voluntary locomotor activity was assessed 6 and 24 h after the challenge. Plasma and tissues were collected 0, 6 or 24 h after the challenge for analysis. Histological analysis of intestinal samples included evaluation of villi length and width, lamina propria (LP) width, crypt depth and intraepithelial as well as LP leukocyte numbers. Plasma was analyzed for IL-1β, IL-4, IL-6, IL-10, IL-12p40, IL-12p70, interferon gamma and tumor necrosis factor α. Diet did not affect BW and feed intake. The LPS challenge led to decreased voluntary locomotor activity (Pb.05). Moderate Zn restriction led to greater leukocyte infiltration in the LP after the LPS challenge (Pb.05) and higher plasma IL-6 and IL-10 levels 24 h after the LPS challenge (Pb.01). Results indicate that Zn status impacts intestinal responses to LPS through modulation of the cytokine response and leukocyte recruitment, and this impact is evident even with short-term (4 weeks) moderate Zn restriction.

Supplementation of diets for lactating sows with zinc amino acid complex and gastric nutriment-intubation of suckling pigs with zinc methionine on mineral status, intestinal morphology and bacterial translocation in lipopolysaccharide-challenged weaned pigs

“…This morphological change may be indicative of an endotoxin challenge. However, no effect of LPS challenge on villus width was reported for a recent study with mice (Peterson et al., 2008).…”

The ubiquitous role of zinc in health and disease

“…119 Zinc induces growth factors, promotes cell proliferation, and stimulates the synthesis of proteins involved in mucosal turnover, tissue healing, and repair. 81,[119][120][121] Zinc may also reduce adhesion and internalization of some pathogenic bacteria. 122 Diarrhea and decreased appetite are characteristic symptoms of zinc deficiency in mammals.…”

Nutraceutical Properties of Milk Fat Globular Membrane

“…Mice were fed experimental diets for five weeks. This timeframe is precedented by a previous investigation examining dietary Zn and LPS induced inflammation (Peterson et al 2008). …”

“…This dose of LPS (i.p.) has previously been shown to induce monocyte adhesion and infiltration into intestinal tissues of mice and induce intestinal distress (Peterson et al 2008). To assess intestinal permeability, mice were gavaged with 4000 Da Dextran-FITC (Sigma) suspended in PBS immediately after vehicle control or LPS injection (Krimsky et al 2000).…”