Induction of systemic immunologic tolerance to β-lactoglobulin by oral administration of a whey protein hydrolysate

Background: Oral administration of an antigen has been shown to suppress 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: The purpose of this study was to determine whether oral tolerance can be induced with protein peptides. Partially hydrolyzed and extensively hydrolyzed cow's milk formulas were compared for their capacity to induce 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 β-lactoglobulin and ovalbumin on day 5 and bled on day 19. Sera were analyzed for specific IgE and IgG antibodies by ELISA and for functional IgE response by in vitro mast cell mediator (tritiated serotonin) release. In vivo modulation of intestinal mast cells was analyzed by the specific release of the rat mast cell protease II, and T-cell response was determined by tritiated thymidine incorporation into lymph node lymphocytes. Results: Oral administration of a partially hydrolyzed cow's milk formula suppresses specific serum IgE and IgG anti-β-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 extensively hydrolyzed formula was unable to achieve the induction of such an oral tolerance. Conclusion: These results support the view that partially hydrolyzed proteins are able to induce specific oral tolerance, whereas extensively hydrolyzed proteins are not. (J Allergy Clin Immunol 1997;100:266-73.)