Dose-dependent food allergy induction against ovalbumin under acid-suppression: a murine food allergy model.
BACKGROUND
Animal models are essential for analyzing the allergenic potential of food proteins and for investigating mechanisms underlying food allergy. Based on previous studies revealing acid-suppression medication as risk factor for food allergy induction, we aimed to establish a mouse model mimicking the natural route of sensitization in patients.


METHODS
The effect of acid-suppressing medication on murine gastric pH was assessed by intragastric pH measurements after two injections of a proton pump inhibitor (PPI). To investigate dose-dependency, mice were fed different concentrations of ovalbumin (OVA; 0.2, 0.5, 1.0, 2.5 or 5.0mg) either with or without anti-ulcer medication. Additionally, different routes of exposure (i.p. vs. oral) were compared in a second immunization experiment. Sera were screened for OVA-specific antibody titers (IgG1, IgG2a and IgE) in ELISA and RBL assay. Clinical reactivity was evaluated by measuring rectal temperature after oral challenge and by type I skin tests.


RESULTS
Two intravenous injections of PPI significantly elevated the gastric pH from 2.97 to 5.3. Only oral immunization with 0.2mg OVA under anti-acid medication rendered elevated IgG1, IgG2a and IgE titers compared to all other concentrations. Protein feeding alone altered antibody titers only marginally. Even though also i.p. immunizations induced high levels of specific IgE, only oral immunizations under anti-acids induced anaphylactic reactions evidenced by a significant decrease of body temperature.


CONCLUSIONS
Only low-dosage ovalbumin feedings under anti-acid medication resulted in IgE mediated food allergy. Based on this knowledge we have established a suitable food allergy model for further investigations of food adverse reactions.
Diesner
S C
SC
Department of Pathophysiology, Center of Physiology, Pathophysiology and Immunology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.
Knittelfelder
R
R
Krishnamurthy
D
D
Pali-Schöll
I
I
Gajdzik
L
L
Jensen-Jarolim
E
E
Untersmayr
E
E
D000284:Administration, Oral; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D005512:Food Hypersensitivity / Q000097:blood / Q000276:immunology*; D005745:Gastric Acidity Determination; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000032:analysis / Q000276:immunology; D015848:Interleukin-5 / Q000032:analysis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology*; D054328:Proton Pump Inhibitors / Q000494:pharmacology; D012882:Skin Tests
D007074:Immunoglobulin G; D015848:Interleukin-5; D054328:Proton Pump Inhibitors; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin