Ingestion of Casein Hydrolysate Induces Oral Tolerance and Suppresses Subsequent Epicutaneous Sensitization and Development of Anaphylaxis Reaction to Casein in Mice.

Casein is the most dominant causal allergen in cow's milk allergy (CMA). Casein hydrolysates are frequently applied in infant formulas for children with a risk or history of CMA. However, there is limited information on the oral tolerance-inducing ability of casein hydrolysates.The aim of this study was to investigate whether the ingestion of casein hydrolysate induces tolerance to casein, ultimately preventing subsequent epicutaneous sensitization and development of an anaphylaxis reaction.BALB/c mice were orally administered casein or a casein hydrolysate (CNH) via the drinking water and were then epicutaneously sensitized by repeated exposure of casein on tape-stripped skin. Sensitization was assessed by basophil activation tests, the serum levels of casein-specific antibodies, and cytokine production from casein-stimulated spleen and mesenteric lymph node (MLN) cells. Occurrence of an anaphylaxis reaction was evaluated by measuring rectal temperature and the plasma level of mouse mast cell protease-1 (mMCP-1) after oral casein challenges. The T cell population in the spleen and MLN was assessed by flow cytometry. Intestinal mast cells and basophils were analyzed histologically.Sensitization and anaphylaxis reaction to casein were significantly suppressed in casein- or CNH-fed mice compared to controls. Prior ingestion of casein or CNH had no effect on the population of regulatory T cells and activated T cells in lymphoid tissues. Intestinal basophils increased by the epicutaneous sensitization of casein, which was suppressed in casein- or CNH-fed mice. Although the increase in the plasma level of mMCP-1 after oral challenge was suppressed in casein- or CNH-fed mice, there was no change in the number of intestinal mast cells.Prior ingestion of casein or CNH induced oral tolerance and suppressed subsequent epicutaneous sensitization and development of systemic anaphylaxis to casein.