casein-hydrolysate and Hypersensitivity

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.

Topics: Administration, Cutaneous; Allergens; Animals; Basophils; Caseins; Eating; Female; Hypersensitivity; Immune Tolerance; Mast Cells; Mice, Inbred BALB C; T-Lymphocytes, Regulatory

Around 2.5% of neonates experience hypersensitivity reactions to cow's milk protein during the first year of life, which is highly associated with early exposure to cow's milk. To prevent early allergy development, cow's milk proteins in infant formulas were modified by hydrolyzation processes for use in children at high atopic risk who need milk supplementation in the first months of life. Dependent on the degree of modification, hydrolyzed cow's milk formulas are differentiated into extensively and partially hydrolyzed whey or casein hydrolysates (pHF, eHF). However, their allergy-preventive potential seems not only to dependent on the degree but also on the process of hydrolysis. pHF and eHF can be used for primary prevention of allergy in infants at high atopic risk, while only eHFs are indicated for secondary prevention in patients with manifest cow's milk allergy. In clinical trials a consistent trend to a reduction in atopy, mainly atopic eczema and food allergy, by certain pHFs and eHFs could be demonstrated in children with a familial risk of atopy until the age of 6 years. Because more than 50% of allergic children do not have a family history of atopy, it would be worthwhile to consider primary allergy prevention with hydrolysates for all children who need supplementation to breastfeeding.

Topics: Animals; Caseins; Child; Child, Preschool; Clinical Trials as Topic; Dermatitis, Atopic; Food Hypersensitivity; Humans; Hypersensitivity; Immune Tolerance; Infant; Infant Formula; Infant, Newborn; Milk Hypersensitivity; Milk Proteins; Models, Animal; Nutrition Policy; Protein Hydrolysates