A murine model of IgE-mediated cow's milk hypersensitivity

Background: Cow's milk allergy (CMA) is one of the leading causes of food a llergy in children. Understanding the mechanisms involved in the developmen t of CMA has been hampered by the lack of suitable animal models. Objective: We sought to develop a mouse model of IgE-mediated cow's milk hy persensitivity (CMH) that mimics the clinical features of immediate CMA in humans. Methods: Three-week-old C3H/HeJ mice were sensitized by intragastric admini stration of cow's milk (CM) plus cholera toxin and boosted 5 times at weekl y intervals. Results: Chi-specific IgE antibody levels were significantly increased at 3 weeks and peaked at 6 weeks after the initial feeding, Intragastric challe nge with Chi at week 6 elicited systemic anaphylaxis accompanied by vascula r leakage, significantly increased plasma histamine, and increased intestin al permeability to casein, Histologic examination of intestinal tissue reve aled marked vascular congestion, edema, and sloughing of enterocytes. The r ole of IgE in mediating CMH was confirmed by abrogation of passive cutaneou s anaphylaxis reactions by heat inactivation of immune sera. Development of IgE-mediated CMH in this model is likely to be T-H2 cell mediated because in vitro stimulation of spleen cells from mice allergic to CM induced signi ficant increases in the levels of IL-4 and IL-5, but not IFN-gamma. Conclusion: This model should provide a useful tool for evaluating the immu nopathogenic mechanisms involved in CMA and for exploring new therapeutic a pproaches.