INDUCTION OF SYSTEMIC IMMUNOLOGICAL-TOLERANCE TO BETA-LACTOGLOBULIN BY ORAL-ADMINISTRATION OF A WHEY-PROTEIN HYDROLYSATE

Background: Oral administration of an antigen has been shown to suppre ss the specific immune response to this antigen. This approach, called oral tolerance, has been demonstrated with intact proteins in animal models for prevention of allergy and autoimmune diseases, Objective: T he purpose of this study was to determine whether oral tolerance can b e induced, with protein peptides, Partially hydrolyzed and extensively hydrolyzed cow's milk formulas were compared for their capacity to in duce tolerance to cow's milk proteins. Methods: Five-week-old Sprague- Dawley rats were fed cow's milk formulas ad libitum from day 1 to day 19. All animals were immunized with beta-lactoglobulin and ovalbumin o n day 5 and bled on day 19. Sera were analyzed for specific IgE and Ig G antibodies by ELISA and for functional IgE response by in vitro mast cell mediator (tritiated serotonin) release, In vivo modulation of in testinal mast cells was analyzed by the specific release of the rat ma st cell protease II, and T-cell response was determined by tritiated t hymidine incorporation into lymph node lymphocytes. Results: Oral admi nistration of a partially hydrolyzed cow's milk formula suppresses spe cific serum IgE and Ige anti-beta-lactoglobulin antibodies, as well as mediator release from rat mast cells and T-lymphocyte response, This suppression was shown to be antigen-specific and dose-dependent. An ex tensively hydrolyzed formula was unable to achieve the induction of su ch an oral tolerance, Conclusion: These results support the view that partially hydrolyzed proteins are able to induce specific oral toleran ce, whereas extensively hydrolyzed proteins are not.