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A protective effect of breast-feeding against the development of celiac disease has been described, but the nature and effects of the actual milk components have not been established. Epidermal growth factor (EGF), a milk cytokine affecting the proliferation and differentiation of mucosal epithelial cells, was studied as to its potential protective effect on the damage of intestinal mucosa by gliadin in a model system.Enteropathy was induced by gliadin in inbred AVN strain rat pups delivered by cesarean section, breast-fed, or hand-fed a milk formula. All experimental groups were treated with interferon-γ (1,000 U per animal, administered intraperitoneally) after birth. Gliadin (0.5 and 3 mg) was intragastrically administered to the pups on days 0 and 3, and a 30-mg challenge dose was given on day 20 (24 hours before the termination of the experiment). One group of artificially fed pups received EGF (100 ng/ml) continuously in the diet.Gliadin- and interferon-γ–treated formula-fed rat pups showed villus atrophy, increase of inflammatory cells, including CD4+ T lymphocytes in the lamina propria, and damage to epithelial tight junctions and the enterocyte brush border. Morphometrically, the villus height was significantly less than in other groups. Recombinant EGF was markedly increased in the epithelial cells of injured jejunum. The intestinal mucosa of gliadin- and interferon-γ–treated pups kept on a EGF-supplemented artificial diet resembled that of breast-fed pups.Pathologic changes in jejunal mucosa (villus atrophy and inflammation) resembling gliadin-induced atrophy appeared on administration of interferon-γ and gliadin to rat pups fed an artificial milk diet immediately after birth. Addition of EGF to the diet protected the rats against pathologic mucosal changes.