Volume 28, Issue 3 pp. 230-237
Original Article

Extensively hydrolyzed casein formula alone or with L. rhamnosus GG reduces β-lactoglobulin sensitization in mice

Rosita Aitoro

Rosita Aitoro

Department of Translational Medical Science, University of Naples ‘Federico II’, Naples, Italy

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Raffaele Simeoli

Raffaele Simeoli

Department of Pharmacy, University of Naples ‘Federico II’, Naples, Italy

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Antonio Amoroso

Antonio Amoroso

Department of Translational Medical Science, University of Naples ‘Federico II’, Naples, Italy

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Lorella Paparo

Lorella Paparo

Department of Translational Medical Science, University of Naples ‘Federico II’, Naples, Italy

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Rita Nocerino

Rita Nocerino

Department of Translational Medical Science, University of Naples ‘Federico II’, Naples, Italy

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Claudio Pirozzi

Claudio Pirozzi

Department of Pharmacy, University of Naples ‘Federico II’, Naples, Italy

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Margherita di Costanzo

Margherita di Costanzo

Department of Translational Medical Science, University of Naples ‘Federico II’, Naples, Italy

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Rosaria Meli

Rosaria Meli

Department of Pharmacy, University of Naples ‘Federico II’, Naples, Italy

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Carmen De Caro

Carmen De Caro

Department of Pharmacy, University of Naples ‘Federico II’, Naples, Italy

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Gianluca Picariello

Gianluca Picariello

Institute of Food Sciences, CNR, Avellino, Italy

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Gianfranco Mamone

Gianfranco Mamone

Institute of Food Sciences, CNR, Avellino, Italy

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Antonio Calignano

Antonio Calignano

Department of Pharmacy, University of Naples ‘Federico II’, Naples, Italy

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Cathryn R. Nagler

Cathryn R. Nagler

Committee on Immunology and Departments of Pathology, University of Chicago, Chicago, IL, USA

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Roberto Berni Canani

Corresponding Author

Roberto Berni Canani

Department of Translational Medical Science, University of Naples ‘Federico II’, Naples, Italy

European Laboratory for The Investigation of Food Induced Diseases, University of Naples ‘Federico II’, Naples, Italy

CEINGE Advanced Biotechnologies, University of Naples ‘Federico II’, Naples, Italy

Correspondence

Roberto Berni Canani, Pediatric Allergy Program - Department of Translational Medical Science, European Laboratory for The Investigation of Food Induced Diseases, and CEINGE Advanced Biotechnologies, University of Naples ‘Federico II’, Via Sergio Pansini, 5, Naples 80131, Italy

Tel.: +390817462680

Fax: +390817462375-4228

E-mail: [email protected]

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First published: 19 December 2016
Citations: 33

Abstract

Background

Extensively hydrolyzed casein formula (EHCF) has been proposed for the prevention and is commonly used for the treatment of cow's milk allergy (CMA). The addition of the probiotic Lactobacillus rhamnosus GG (LGG) to EHCF may induce faster acquisition of tolerance to cow's milk. The mechanisms underlying this effect are largely unexplored. We investigated the effects of EHCF alone or in combination with LGG on β-lactoglobulin (BLG) sensitization in mice.

Methods

Three-week-old C3H/HeOuJ mice were sensitized by oral administration of BLG using cholera toxin as adjuvant at weekly intervals for 5 weeks (sensitization period). Two experimental phases were conducted: (i) EHCF or EHCF+LGG given daily, starting 2 weeks before the sensitization period and then given daily for 5 weeks and (ii) EHCF or EHCF+LGG given daily for 4 weeks, starting 1 week after the sensitization period. Diet free of cow's milk protein was used as control. Acute allergic skin response, anaphylactic symptom score, body temperature, intestinal permeability, anti-BLG serum IgE, and interleukin (IL)-4, IL-5, IL-10, IL-13, IFN-γ mRNA expression were analyzed. Peptide fractions of EHCF were characterized by reversed-phase (RP)-HPLC, MALDI-TOF mass spectrometry, and nano-HPLC/ESI-MS/MS.

Results

Extensively hydrolyzed casein formula administration before or after BLG-induced sensitization significantly reduced acute allergic skin reaction, anaphylactic symptom score, body temperature decrease, intestinal permeability increase, IL-4, IL-5, IL-13, and anti-BLG IgE production. EHCF increased expression of IFN-γ and IL-10. Many of these effects were significantly enhanced by LGG supplementation. The peptide panels were similar between the two study formulas and contained sequences that could have immunoregulatory activities.

Conclusions

The data support dietary intervention with EHCF for CMA prevention and treatment through a favorable immunomodulatory action. The observed effects are significantly enhanced by LGG supplementation.

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