title: Allergic responses induced by goat milk αS1-casein in a murine model of gastrointestinal atopy.
abstract: 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 α(S1)-casein (CN). Studies suggest that goat milk with low levels of α(S1)-CN may reduce allergenicity of milk, but the dose response to α(S1)-CN has not been confirmed. In this study, we examined the immune response to varying levels of goat α(S1)-CN in a mouse model of gastrointestinal allergy. BALB/c mice (aged 5 wk) were given intraperitoneal injections with α(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 20mg of α(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-γ responses to 48-h activation with antigen were measured in cultured splenocytes. We determined that mice sensitized with α(S1)-CN had higher titers of specific IgG(1) and IgE antibodies compared with controls; however, groups challenged with differing doses of α(S1)-CN did not differ. The group challenged with the highest dose of α(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 α(S1)-CN. Overall, α(S1)-CN stimulated the production of cytokines associated with allergic disease in a dose-dependent manner. Thus, milk with lower levels of α(S1)-CN should contribute to a lesser antigenic burden.
authors.affiliation: AgResearch Ruakura, Hamilton, New Zealand. ali.hodgkinson@agresearch.co.nz
authors.forename: A J
authors.initials: AJ
authors.lastname: Hodgkinson
authors.forename: N A
authors.initials: NA
authors.lastname: McDonald
authors.forename: L J
authors.initials: LJ
authors.lastname: Kivits
authors.forename: D R
authors.initials: DR
authors.lastname: Hurford
authors.forename: S
authors.initials: S
authors.lastname: Fahey
authors.forename: C
authors.initials: C
authors.lastname: Prosser
mesh_terms: D000818:Animals; D002364:Caseins / Q000276:immunology* / Q000494:pharmacology; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000276:immunology*; D006041:Goats; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D016269:Milk Hypersensitivity / Q000209:etiology* / Q000276:immunology
chemical_list: D002364:Caseins; D007074:Immunoglobulin G; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma