Enteral Feeding Preserves Gut Th‐2 Cytokines Despite Mucosal Cellular Adhesion Molecule‐1 Blockade

Abstract

Background: Parenteral nutrition (PN) decreases gut‐associated lymphoid tissue (GALT), the intestinal IgA stimulating cytokines IL‐4 and IL‐10 in gut homogenates, intestinal IgA levels and the expression of Peyer patch (PP) mucosal cellular adhesion molecule‐1 (MAdCAM‐1), an adhesion molecule found on the high endothelial venules of PP and other tissues. IL‐4 in PP stimulates MAdCAM expression in vitro. MAdCAM‐1 blockade with MECA‐367 reduces GALT cell populations to PN levels but maintains intestinal IgA levels if the animals are chow fed. This study compares IL‐4 levels in PP of chow and PN fed mice and measures the effects of MAdCAM blockade on IL‐4 and IL‐10 levels in gut homogenates of chow fed mice. We hypothesized that in vivo IL‐4 levels drop in PP of PN fed mice and IL‐4 and IL‐10 levels are maintained after MAdCAM‐1 blockade in chow fed mice. Methods: Exp 1: 18 mice received chow or PN for 5 days to determine PP IL‐4 levels. Exp 2: 44 mice were randomized to chow + control monoclonal antibody (mAb), chow + MECA‐367 (anti‐MAdCAM‐1 mAb) or PN for 4 days before measurement of IL‐4 and IL‐10 levels in gut homogenates. Results: Exp 1: IL‐4 levels in vivo were lower in PP of PN‐fed mice than chow fed mice (92.0 ± 15.1 pg/mL vs 251.1 ± 14.8, p = .0003). Exp 2: IL‐4 levels were significantly higher in chow + control mAb (187.1 ± 44.1 pg/mL) and chow + MECA‐367 (110.9 ± 19.1 pg/mL) groups than PN mice (21.8 ± 30.6 pg/mL, p < .02 vs chow + control or chow + MECA‐367). IL‐10 levels were significantly lower with PN (23.1 ± 40.9 pg/mL) with chow+control (174.0 ± 22.2 pg/mL p < .01), or chow + MECA‐367 (181.7 ± 23.1 pg/mL, p < .02 vs PN). Conclusions: PN‐feeding reduces in vivo IL‐4 levels in PP (consistent with lowered MAdCAM‐1 expression) and IL‐4 and IL‐10 levels in gut homogenates compared with chow. Despite MAdCAM‐1 blockade, enteral feeding preserved gut IL‐4 levels and increased IL‐10 levels consistent with preserved IgA levels.