Ingestion of partially hydrolyzed whey protein suppresses epicutaneous sensitization to β‐lactoglobulin in mice

Abstract Background Epicutaneous sensitization to food allergens can occur through defective skin barriers. However, the relationship between oral tolerance and epicutaneous sensitization remains to be elucidated. We aimed to determine whether prior oral exposure to whey proteins or their hydrolysates prevents epicutaneous sensitization and subsequent food‐allergic reaction to the whey protein, β‐lactoglobulin (β‐ LG ), and investigated the underlying mechanisms. Methods BALB /c mice were given whey protein concentrate ( WPC ), two kinds of partial whey protein hydrolysate ( PWH 1 or PWH 2), or extensive whey protein hydrolysate ( EWH ) in drinking water for 21 days. The mice were then epicutaneously sensitized with β‐ LG on tape‐stripped skin. Sensitization was assessed by basophil activation tests and by measuring the level of serum β‐ LG ‐specific antibodies and cytokines secreted from β‐ LG ‐restimulated spleen and mesenteric lymph node ( MLN ) cells. Development of an allergic reaction was assessed by monitoring body temperature and by measuring mast cell protease‐1 level in plasma after the β‐ LG oral challenge. Activated T‐cell population among β‐ LG ‐restimulated MLN cells was also analyzed. Results In mice fed with WPC , PWH 1, or PWH 2, sensitization and the development of an allergic reaction were totally reduced. The acceleration of cytokine release from the spleen and MLN cells or T‐cell activation was not evident after β‐ LG restimulation. In EWH ‐fed mice, a suppressive effect, though milder than that in WPC ‐, PWH 1‐, or PWH 2‐fed mice, was observed during the development of the allergic reaction. Conclusions Prior oral exposure to partially hydrolyzed whey protein prevents epicutaneous sensitization and subsequent allergic response to β‐ LG in mice.