Preclinical Brown Norway Rat Models for the Assessment of Infant Formulas in the Prevention and Treatment of Cow's Milk Allergy

Louise Heydenreich Jensen, Jeppe Madura Larsen, Charlotte Bernhard Madsen, R. R. Laursen, Lotte Neergaard Jacobsen, Katrine Lindholm Bøgh*

*Corresponding author for this work

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Abstract

Background: Infant formulas (IFs) based on hydrolysed cow's milk proteins are central in the management of cow's milk allergy (CMA) in infants and small children. New IF compositions with improved prevention and treatment properties are needed, along with appropriate preclinical animal models, to evaluate these properties before introduction into humans. Objectives: We aimed to develop preclinical models for the assessment of the primary preventive and desensitising capacity of cow's milk IF in allergy-prone, high-IgE responder Brown Norway rats. Method: Preventive capacity was assessed in cow's milk-naïve rats given a 2- or 4-week regimen of whey-based extensively hydrolysed IF (eHF), partially hydrolysed IF (pHF), or intact β-lactoglobulin (BLG) ad libitum in drinking bottles, followed by intraperitoneal (i.p.) immunisation with BLG. Desensitising capacity was assessed in orally BLG-sensitised rats after a 3- or 6-week regimen of eHF, pHF, or intact BLG administration in drinking bottles, followed by i.p. challenge with BLG. Primary preventive and desensitising capacity were analysed by serum BLG-specific IgG1 and IgE. Results: The preventive regimens did not induce detectable BLG-specific IgG1 or IgE in cow's milk-naïve rats. A preventive regimen consisting of pHF or BLG, but not eHF, induced complete tolerance to BLG, as demonstrated by the absence of BLG-specific IgE following i.p. immunisation. Desensitising regimens had a limited effect on BLG-specific IgG1 or IgE when comparing sensitised rats before and after treatment. Challenge with BLG (i.p.) increased BLG-specific IgE in all treatment regimens except for in the BLG group, suggesting a limited desensitising capacity of IF based on hydrolysates and a need for the presence of intact allergen for desensitisation. Conclusions: The presented models highlight that different mechanisms are at play in the induction of de novo tolerance to cow's milk proteins and the desensitisation of CMA. Different IF products may be needed for the primary prevention and treatment of CMA.

Original languageEnglish
JournalInternational Archives of Allergy and Immunology
Volume178
Issue number4
Pages (from-to)307-314
ISSN1018-2438
DOIs
Publication statusPublished - 2019

Keywords

  • Animal models
  • Food allergy
  • Infant formula
  • Milk

Cite this

@article{90b94f6e653e49458052b399d5c6f976,
title = "Preclinical Brown Norway Rat Models for the Assessment of Infant Formulas in the Prevention and Treatment of Cow's Milk Allergy",
abstract = "Background: Infant formulas (IFs) based on hydrolysed cow's milk proteins are central in the management of cow's milk allergy (CMA) in infants and small children. New IF compositions with improved prevention and treatment properties are needed, along with appropriate preclinical animal models, to evaluate these properties before introduction into humans. Objectives: We aimed to develop preclinical models for the assessment of the primary preventive and desensitising capacity of cow's milk IF in allergy-prone, high-IgE responder Brown Norway rats. Method: Preventive capacity was assessed in cow's milk-na{\"i}ve rats given a 2- or 4-week regimen of whey-based extensively hydrolysed IF (eHF), partially hydrolysed IF (pHF), or intact β-lactoglobulin (BLG) ad libitum in drinking bottles, followed by intraperitoneal (i.p.) immunisation with BLG. Desensitising capacity was assessed in orally BLG-sensitised rats after a 3- or 6-week regimen of eHF, pHF, or intact BLG administration in drinking bottles, followed by i.p. challenge with BLG. Primary preventive and desensitising capacity were analysed by serum BLG-specific IgG1 and IgE. Results: The preventive regimens did not induce detectable BLG-specific IgG1 or IgE in cow's milk-na{\"i}ve rats. A preventive regimen consisting of pHF or BLG, but not eHF, induced complete tolerance to BLG, as demonstrated by the absence of BLG-specific IgE following i.p. immunisation. Desensitising regimens had a limited effect on BLG-specific IgG1 or IgE when comparing sensitised rats before and after treatment. Challenge with BLG (i.p.) increased BLG-specific IgE in all treatment regimens except for in the BLG group, suggesting a limited desensitising capacity of IF based on hydrolysates and a need for the presence of intact allergen for desensitisation. Conclusions: The presented models highlight that different mechanisms are at play in the induction of de novo tolerance to cow's milk proteins and the desensitisation of CMA. Different IF products may be needed for the primary prevention and treatment of CMA.",
keywords = "Animal models, Food allergy, Infant formula, Milk",
author = "Jensen, {Louise Heydenreich} and Larsen, {Jeppe Madura} and Madsen, {Charlotte Bernhard} and Laursen, {R. R.} and Jacobsen, {Lotte Neergaard} and B{\o}gh, {Katrine Lindholm}",
year = "2019",
doi = "10.1159/000495801",
language = "English",
volume = "178",
pages = "307--314",
journal = "International Archives of Allergy and Immunology",
issn = "1018-2438",
publisher = "S. Karger AG",
number = "4",

}

Preclinical Brown Norway Rat Models for the Assessment of Infant Formulas in the Prevention and Treatment of Cow's Milk Allergy. / Jensen, Louise Heydenreich; Larsen, Jeppe Madura; Madsen, Charlotte Bernhard; Laursen, R. R.; Jacobsen, Lotte Neergaard; Bøgh, Katrine Lindholm.

In: International Archives of Allergy and Immunology, Vol. 178, No. 4, 2019, p. 307-314.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Preclinical Brown Norway Rat Models for the Assessment of Infant Formulas in the Prevention and Treatment of Cow's Milk Allergy

AU - Jensen, Louise Heydenreich

AU - Larsen, Jeppe Madura

AU - Madsen, Charlotte Bernhard

AU - Laursen, R. R.

AU - Jacobsen, Lotte Neergaard

AU - Bøgh, Katrine Lindholm

PY - 2019

Y1 - 2019

N2 - Background: Infant formulas (IFs) based on hydrolysed cow's milk proteins are central in the management of cow's milk allergy (CMA) in infants and small children. New IF compositions with improved prevention and treatment properties are needed, along with appropriate preclinical animal models, to evaluate these properties before introduction into humans. Objectives: We aimed to develop preclinical models for the assessment of the primary preventive and desensitising capacity of cow's milk IF in allergy-prone, high-IgE responder Brown Norway rats. Method: Preventive capacity was assessed in cow's milk-naïve rats given a 2- or 4-week regimen of whey-based extensively hydrolysed IF (eHF), partially hydrolysed IF (pHF), or intact β-lactoglobulin (BLG) ad libitum in drinking bottles, followed by intraperitoneal (i.p.) immunisation with BLG. Desensitising capacity was assessed in orally BLG-sensitised rats after a 3- or 6-week regimen of eHF, pHF, or intact BLG administration in drinking bottles, followed by i.p. challenge with BLG. Primary preventive and desensitising capacity were analysed by serum BLG-specific IgG1 and IgE. Results: The preventive regimens did not induce detectable BLG-specific IgG1 or IgE in cow's milk-naïve rats. A preventive regimen consisting of pHF or BLG, but not eHF, induced complete tolerance to BLG, as demonstrated by the absence of BLG-specific IgE following i.p. immunisation. Desensitising regimens had a limited effect on BLG-specific IgG1 or IgE when comparing sensitised rats before and after treatment. Challenge with BLG (i.p.) increased BLG-specific IgE in all treatment regimens except for in the BLG group, suggesting a limited desensitising capacity of IF based on hydrolysates and a need for the presence of intact allergen for desensitisation. Conclusions: The presented models highlight that different mechanisms are at play in the induction of de novo tolerance to cow's milk proteins and the desensitisation of CMA. Different IF products may be needed for the primary prevention and treatment of CMA.

AB - Background: Infant formulas (IFs) based on hydrolysed cow's milk proteins are central in the management of cow's milk allergy (CMA) in infants and small children. New IF compositions with improved prevention and treatment properties are needed, along with appropriate preclinical animal models, to evaluate these properties before introduction into humans. Objectives: We aimed to develop preclinical models for the assessment of the primary preventive and desensitising capacity of cow's milk IF in allergy-prone, high-IgE responder Brown Norway rats. Method: Preventive capacity was assessed in cow's milk-naïve rats given a 2- or 4-week regimen of whey-based extensively hydrolysed IF (eHF), partially hydrolysed IF (pHF), or intact β-lactoglobulin (BLG) ad libitum in drinking bottles, followed by intraperitoneal (i.p.) immunisation with BLG. Desensitising capacity was assessed in orally BLG-sensitised rats after a 3- or 6-week regimen of eHF, pHF, or intact BLG administration in drinking bottles, followed by i.p. challenge with BLG. Primary preventive and desensitising capacity were analysed by serum BLG-specific IgG1 and IgE. Results: The preventive regimens did not induce detectable BLG-specific IgG1 or IgE in cow's milk-naïve rats. A preventive regimen consisting of pHF or BLG, but not eHF, induced complete tolerance to BLG, as demonstrated by the absence of BLG-specific IgE following i.p. immunisation. Desensitising regimens had a limited effect on BLG-specific IgG1 or IgE when comparing sensitised rats before and after treatment. Challenge with BLG (i.p.) increased BLG-specific IgE in all treatment regimens except for in the BLG group, suggesting a limited desensitising capacity of IF based on hydrolysates and a need for the presence of intact allergen for desensitisation. Conclusions: The presented models highlight that different mechanisms are at play in the induction of de novo tolerance to cow's milk proteins and the desensitisation of CMA. Different IF products may be needed for the primary prevention and treatment of CMA.

KW - Animal models

KW - Food allergy

KW - Infant formula

KW - Milk

U2 - 10.1159/000495801

DO - 10.1159/000495801

M3 - Journal article

VL - 178

SP - 307

EP - 314

JO - International Archives of Allergy and Immunology

JF - International Archives of Allergy and Immunology

SN - 1018-2438

IS - 4

ER -