A murine model of cow's milk protein-induced allergic reaction: use for safety assessment of hidden milk allergens.
BACKGROUND
Masked allergens in processed food products can lead to severe allergic reactions following unintentional ingestion. We sought to develop a murine model for the detection of hidden cow's milk proteins (CMP). This study aimed to induce cow's milk allergy in mice, to characterize the anaphylaxis induced by CMP in this model, and to validate its reliability using three margarines manufactured with (A) or without (B, C) milk, sharing the same production line.


METHODS
Three-week-old BALB/c mice were sensitized intragastrically with CMP plus cholera toxin and boosted 6 times at weekly intervals. CMP-sensitization status was monitored by skin tests, and measurement of CMP-specific IgE and IgG1 levels. On day 44, the minimal threshold of clinical reactivity to CMP in terms of anaphylaxis was determined by performing a dose response of intraperitoneal CMP challenge. Under the same conditions, anaphylaxis was evaluated in CMP-sensitized mice after challenge with protein extracts of margarines A, B or C.


RESULTS
Sensitization to CMP was demonstrated by positive skin tests and increased CMP-specific IgE and IgG1. The minimal clinical reactivity threshold corresponding to 0.1 mg CMP elicited detectable anaphylaxis evidenced by clinical symptoms, a decrease in breathing frequency, and increased plasma histamine upon challenge. Similarly, challenges with margarine A containing CMP demonstrated anaphylaxis, whereas those with B or C did not elicit any detectable allergic reaction.


CONCLUSIONS
This study shows that our murine model of CMP-induced anaphylaxis is useful for investigating the allergenic activity and the assessment of margarines with respect to milk.
Proust
B
B
Department of Internal Medicine, Clinical Immunology and Allergology, University of Nancy, France.
Astier
C
C
Renaudin
J M
JM
Magueur
E
E
Maurice
D
D
Belcourt
C
C
Yen
F T
FT
Kanny
G
G
Bihain
B E
BE
Jacquenet
S
S
D000485:Allergens / Q000737:chemistry / Q000276:immunology*; D000707:Anaphylaxis; D000818:Animals; D001944:Breath Tests; D002772:Cholera Toxin / Q000276:immunology; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005504:Food Analysis / Q000379:methods; D006801:Humans; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D008383:Margarine / Q000009:adverse effects* / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D008892:Milk / Q000009:adverse effects*; D016269:Milk Hypersensitivity / Q000178:diet therapy / Q000276:immunology* / Q000503:physiopathology; D008894:Milk Proteins / Q000737:chemistry / Q000276:immunology*; D012882:Skin Tests
D000485:Allergens; D008894:Milk Proteins; D007073:Immunoglobulin E; D008383:Margarine; D002772:Cholera Toxin