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

PLoS One. 2015 Apr 29;10(4):e0125314. doi: 10.1371/journal.pone.0125314. eCollection 2015.

Abstract

Background: Food 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.

Objective: The 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.

Methods: Rats 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.

Results: Serum 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.

Conclusions: These 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood*
  • Bordetella pertussis / immunology
  • Bordetella pertussis / pathogenicity
  • Disease Models, Animal
  • Food Hypersensitivity / blood*
  • Food Hypersensitivity / immunology
  • Food Hypersensitivity / physiopathology
  • Gene Expression Regulation
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin E / blood
  • Immunoglobulin G / blood
  • Intestines / drug effects
  • Intestines / immunology
  • Ovalbumin / administration & dosage*
  • Ovalbumin / immunology
  • Rats
  • Serine Endopeptidases / biosynthesis
  • Serine Endopeptidases / blood*

Substances

  • Biomarkers
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin E
  • Ovalbumin
  • Serine Endopeptidases
  • cytotoxic T lymphocyte-specific serine protease

Grants and funding

This study was supported by grants from the Spanish Ministries of Science and Innovation (AGL2008-02790) and Economy and Competitivity (AGL2011-24279). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.