ORAL TRANSFORMING GROWTH-FACTOR-ALPHA ENHANCES JEJUNAL MUCOSAL RECOVERY AND ELECTRICAL-RESISTANCE IN PIGLET ROTAVIRUS ENTERITIS

A randomized, investigator-masked trial determined the effects of oral recombinant human transforming growth factor-alpha (TGF alpha) on jej unal mucosal recovery in 75 piglets with rotavirus diarrhea. Rotavirus inoculation of artificially reared piglets induced subtotal (similar to 50%) villus atrophy and watery diarrhea. Dietary TGF alpha was asso ciated with significant restoration of villus surface area by 4 d post inoculation (p.i.) and complete restoration by 8 d p.i., whereas salin e-treated animals required 12 d for recovery. Jejunal segments from cl inically recovered TGF alpha-treated piglets showed an increase in ele ctrical resistance across the epithelial barrier in vitro which was pr oportional to villus height. TGF alpha treatment for 12 d also produce d a 30-50% increase in jejunal mucosal mass (protein content and wet w eight), compared with the corresponding values in saline-treated pigle ts and in uninfected controls. However, oral TGF alpha did not hasten the resolution of diarrhea, enhance the specific activities of jejunal mucosal digestive enzymes, or increase jejunal glucose-stimulated Na absorption in vitro. We conclude that dietary TGF alpha stimulates je junal mucosal hypertrophy, improves barrier function, and enhances reg rowth of villi in rotavirus enteritis; however, it does not facilitate the restoration of functional activity or mucosal digestive enzymes. Oral TGF alpha can facilitate intestinal epithelial recovery in diseas es associated with mucosal damage.