U.S. Department of Defense


Date of this Version



Published in Journal of Nutritional Biochemistry, 19, (2008), 193–199


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 (P <.05). Moderate Zn restriction led to greater leukocyte infiltration in the LP after the LPS challenge (P <.05) and higher plasma IL-6 and IL-10 levels 24 h after the LPS challenge (P <.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.