Allergic responses induced by goat milk αS1-casein in a murine model of gastrointestinal atopy

Up to 3% of young children develop milk allergy and this may influence the development of immune-mediated diseases in later life. One protein that has been associated with allergic reactions to ruminant milk is alpha(S1)-casein (CN). Studies suggest that goat milk with low levels of alpha(S1)-CN may reduce allergenicity of milk, but the dose response to alpha(S1)-CN has not been confirmed. In this study, we examined the immune response to varying levels of goat alpha(S1)-CN in a mouse model of gastrointestinal allergy. BALB/c mice (aged 5 wk) were given intraperitoneal injections with alpha(S1)-CN and aluminum as adjuvant at 1 and 3 wk to sensitize mice to the antigen. In wk 5, groups of fasting mice (n = 8/group) were challenged 4 times on alternate days by intragastric gavage with saline or 2, 10, or 20 mg of alpha(S1)-CN. Serum levels of specific IgE, IgG(1), and IgG(2a) antibodies and mouse mast cell protease-I were determined. Interleukin-4, IL-10, and IFN-gamma responses to 48-h activation with antigen were measured in cultured splenocytes. We determined that mice sensitized with alpha(S1)-CN had higher titers of specific IgG1 and IgE antibodies compared with controls; however, groups challenged with differing doses of alpha(S1)-CN did not differ. The group challenged with the highest dose of alpha(S1)-CN had a 10-fold increase in mouse mast cell protease-I compared with the group challenged with saline. Both IL-4 and IL-10 were produced in a dose-dependent manner by cultured splenocytes incubated with alpha(S1)-CN. Overall, alpha(S1)-CN stimulated the production of cytokines associated with allergic disease in a dose-dependent manner. Thus, milk with lower levels of alpha(S1)-CN should contribute to a lesser antigenic burden.