Development and characterization of an effective food allergy model in Brown Norway rats.

Mar Abril-Gil,Francisco J Pérez-Cano,Alba Garcia-Just,Margarida Castell,Àngels Franch,Lucienne Chatenoud

doi:10.1371/journal.pone.0125314

Abstract

BackgroundFood allergy (FA) is an adverse health effect produced by the exposure to a given food. Currently, there is no optimal animal model of FA for the screening of immunotherapies or for testing the allergenicity of new foods.ObjectiveThe aim of the present study was to develop an effective and rapid model of FA in Brown Norway rats. In order to establish biomarkers of FA in rat, we compared the immune response and the anaphylactic shock obtained in this model with those achieved with only intraperitoneal immunization.MethodsRats received an intraperitoneal injection of ovalbumin (OVA) with alum and toxin from Bordetella pertussis, and 14 days later, OVA by oral route daily for three weeks (FA group). A group of rats receiving only the i.p. injection (IP group) were also tested. Serum anti-OVA IgE, IgG1, IgG2a, IgG2b and IgA antibodies were quantified throughout the study. After an oral challenge, body temperature, intestinal permeability, motor activity, and mast cell protease II (RMCP-II) levels were determined. At the end of the study, anti-OVA intestinal IgA, spleen cytokine production, lymphocyte composition of Peyer’s patches and mesenteric lymph nodes, and gene expression in the small intestine were quantified.ResultsSerum OVA-specific IgG1, IgG2a and IgG2b concentrations rose with the i.p. immunization but were highly augmented after the oral OVA administration. Anti-OVA IgE increased twofold during the first week of oral OVA gavage. The anaphylaxis in both IP and FA groups decreased body temperature and motor activity, whereas intestinal permeability increased. Interestingly, the FA group showed a much higher RMCP II serum protein and intestinal mRNA expression.ConclusionsThese results show both an effective and relatively rapid model of FA assessed by means of specific antibody titres and the high production of RMCP-II and its intestinal gene expression.

Highlights

Food allergy (FA) is ‘an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food’ [1]
The FA group showed a much higher RMCP II serum protein and intestinal mRNA expression. These results show both an effective and relatively rapid model of FA assessed by means of specific antibody titres and the high production of rat mast cell protease II (RMCP-II) and its intestinal gene expression
The present study aimed to develop an effective and more rapid model of FA in Brown Norway (BN) rats based on that reported by Ogawa et al [43] with only one i.p. injection of the allergen with alum together with toxin from Bordetella pertussis to promote IgE synthesis [44], and two weeks later the oral administration of soluble allergen

Summary

Introduction

Food allergy (FA) is ‘an adverse health effect arising from a specific immune response that occurs reproducibly on exposure to a given food’ [1]. Nowadays it is a major public health problem and the only therapy available consists of avoiding the causative foods [2]. Patients with FA have lost the immune mechanisms responsible for oral tolerance, and recognize some food antigens as harmful molecules. In this population, alterations in Treg cell function and environmental factors, such as microbiota, have been suggested to be important contributors to food sensitization and allergy [11]. There is no optimal animal model of FA for the screening of immunotherapies or for testing the allergenicity of new foods.

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Results

Conclusion