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Dietary medium-chain triglycerides promote oral allergic sensitization and orally induced anaphylaxis to peanut protein in mice - 30/01/13

Doi : 10.1016/j.jaci.2012.10.011 
Jianing Li, MS a, Yu Wang, BS a, Lihua Tang, PhD a, Willem J.S. de Villiers, MD, PhD a, Donald Cohen, PhD b, Jerold Woodward, PhD b, Fred D. Finkelman, MD c, Erik R.M. Eckhardt, PhD a, b,
a Graduate Center for Nutritional Sciences and Internal Medicine Department, Division of Digestive Diseases and Nutrition, University of Kentucky, Lexington, Ky 
b Department of Immunology, Microbiology and Molecular Genetics, University of Kentucky, Lexington, Ky 
c Department of Medicine, Cincinnati Veterans Affairs Medical Center; the Department of Medicine, Division of Immunology, Allergy and Rheumatology, University of Cincinnati College of Medicine; and the Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio 

Corresponding author: Erik R. M. Eckhardt, PhD, Graduate Center for Nutritional Sciences, 588 Charles T. Wethington Building, 900 S Limestone, Lexington, KY 40536-0200.

Abstract

Background

The prevalence of peanut allergies is increasing. Peanuts and many other allergen sources contain significant amounts of triglycerides, which affect absorption of antigens but have unknown effects on sensitization and anaphylaxis. We recently reported that dietary medium-chain triglycerides (MCTs), which bypass mesenteric lymph and directly enter portal blood, reduce intestinal antigen absorption into blood compared with long-chain triglycerides (LCTs), which stimulate mesenteric lymph flow and are absorbed in chylomicrons through mesenteric lymph.

Objective

We sought to test how dietary MCTs affect food allergy.

Methods

C3H/HeJ mice were fed peanut butter protein in MCT, LCT (peanut oil), or LCT plus an inhibitor of chylomicron formation (Pluronic L81). Peanut-specific antibodies in plasma, responses of the mice to antigen challenges, and intestinal epithelial cytokine expression were subsequently measured.

Results

MCT suppressed antigen absorption into blood but stimulated absorption into Peyer patches. A single gavage of peanut protein with MCT, as well as prolonged feeding in MCT-based diets, caused spontaneous allergic sensitization. MCT-sensitized mice experienced IgG-dependent anaphylaxis on systemic challenge and IgE-dependent anaphylaxis on oral challenge. MCT feeding stimulated jejunal-epithelial thymic stromal lymphopoietin, Il25, and Il33 expression compared with that seen after LCT feeding and promoted TH2 cytokine responses in splenocytes. Moreover, oral challenges of sensitized mice with antigen in MCT significantly aggravated anaphylaxis compared with challenges with the LCT. Importantly, the effects of MCTs could be mimicked by adding Pluronic L81 to LCTs, and in vitro assays indicated that chylomicrons prevent basophil activation.

Conclusion

Dietary MCTs promote allergic sensitization and anaphylaxis by affecting antigen absorption and availability and by stimulating TH2 responses.

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Key words : Peanut allergy, triglycerides, thymic stromal lymphopoietin, adjuvant, chylomicrons, intestinal epithelium, TH2 responses

Abbreviations used : LCT, MCT, MLN, OVA, PL81, TSLP


Plan


 Supported by National Institutes of Health grants 5R21AI088605-02 and 5P20RR021954-03 (to E.R.M.E.) and a Merit Award from the US Department of Veterans Affairs (to F.D.F.).
 Disclosure of potential conflict of interest: J. Li has received research support and travel support from the National Institutes of Health (NIH). J. Woodward and E. R. M. Eckhardt have received research support from the NIH. F. D. Finkelman has received consultancy fees from Abbott and has a preliminary patent from the University of Cincinnati. The rest of the authors declare that they have no relevant conflicts of interest.


© 2012  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 131 - N° 2

P. 442-450 - février 2013 Retour au numéro
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