Elevated Intestinal Interleukin-13 Promotes Intestinal Epithelial Barrier Dysfunction

RATIONALE: Experimental investigations suggest that Th2-derived cytokines (IL-4, IL-5, IL-9 and IL-13) are central in the induction of the intestinal manifestations of food allergy. To delineate the contribution of IL13 in intestinal dysfunction we generated intestinal IL-13 transgenic mouse (iIL-13Tg). METHODS: Intestinal permeability [mucosal-serosal flux of FITC-dextran and HRP, and inversely correlating transepithelial resistance (TER)] on isolated jejunum segments from WT and iIL-13Tg mice was measured by an Ussing system. Systemic IL-13, IL-13 Rα2/IL13 complex, and % saturation of IL-13Rα2 were determined by ELISA. Intestinal mast cell levels were quantitated by CAE activity. RESULTS: IIL-13Tg mice had increased serum IL-13 (17.580 ± 2.325 vs 10.540 ± 0.829 ng/ml, p = 0.0357), and reduced % saturation of IL-13Rα2 (14.24% ± 1.393% vs 24.36% ± 2.639%, p = 0.0148) as compared to WT mice, Notably, intestinal mast cell levels (7.683 ± 3.756 vs 4.267 ± 0.3812 mast cells/hpf) were comparable between groups; however iIL-13Tg mice had increased intestinal permeability (TER: 70.03 ± 4.852 vs 134.2 ± 10.64 Ω ∗ cm2, p = 0.0006)], transcellular flux of FITC-dextran (5.708 ± 1.461 vs 1.663 ± 0.565 ng/ml, p < 0.0001) and pararcellular flux of HRP (0.018 ± 0.0033 vs 0.005 ± 0.001 ng/ml, p < 0.0001). CONCLUSIONS: These data demonstrate that intestinal IL-13 regulates intestinal epithelial cell transcellular and paracellular permeability independent of an intestinal mastocytosis.