A diet enriched with cocoa prevents IgE synthesis in a rat allergy model

https://doi.org/10.1016/j.phrs.2012.02.001Get rights and content

Abstract

Previous studies in young rats reported the impact of cocoa intake on healthy immune status and allow suggesting it may have a role in the prevention of some immune-mediated diseases. The aim of this study was to ascertain the effect of a cocoa diet in a model of allergy in young rats. Three-week-old Brown Norway rats were immunized by i.p. injection of ovalbumin (OVA) with alum as adjuvant and Bordetella pertussis toxin. During the next 4 weeks rats received either a cocoa diet (containing 0.2% polyphenols, w/w) or a standard diet. Animals fed a standard diet showed high concentrations of anti-OVA IgG1, IgG2a, IgG2b and high anti-OVA IgE titres, which is the antibody involved in allergic response. In contrast, animals fed a cocoa diet showed significantly lower concentrations of anti-OVA IgG1 and IgG2a antibodies. Interestingly, the cocoa diet prevented anti-OVA IgE synthesis and decreased total serum IgE concentration. Analysis of cytokine production in lymph node cells at the end of the study revealed that, in this compartment, the cocoa diet decreased the tumor necrosis factor (TNF)-α and the interleukin (IL)-10 secretion but not IL-4 production. In conclusion, a cocoa-enriched diet in young rats produces an immunomodulatory effect that prevents anti-allergen IgE synthesis, suggesting a potential role for cocoa flavonoids in the prevention or treatment of allergic diseases.

Introduction

Allergy is a common form of hypersensitivity with an incidence that has increased dramatically in the developed world during the last 50 years and, at present, it affects more than 25% of the population in these countries [1]. Atopic individuals show a dysregulated immune response to non-pathogenic proteins, called allergens, present either in the environment (i.e., dust, pollen, etc.) or in food (i.e., eggs, milk, nuts, etc.). This response starts, like any acquired immune response, with antigenic sensitization. Allergen is taken by dendritic cells and presented to specific Th cells by means of major histocompatibility complex (MHC) class II and co-stimulatory molecules (CD80, CD86, etc.) thus performing the immunological synapse [2]. Activated allergen-specific Th cells, which usually polarize in the Th1 or Th2 effector populations, differentiate and expand into a Th2 subpopulation. Activated Th2 cells produce cytokines such as interleukin (IL)-4, IL-5, IL-10, and IL-13 which are important in switching antibody production from B cells to predominantly IgE production against the allergen, as well as stimulating mast cells and eosinophils. Specific IgE binds then to IgE receptors (FcɛRI) in mast cells; when allergen crosslinks to mast cell-bound IgE, a large number of preformed and newly synthesized mediators and proteases are released and they are responsible for allergic manifestations [3]. Symptoms of allergy affect the skin, respiratory and gastrointestinal systems or even the nervous and cardiovascular systems. The most severe form of allergy is the anaphylaxis, which involves two or more organic systems, sometimes producing an anaphylactic shock with hypotension that can result in death.

At present, the majority of pharmacological agents available for allergies (corticosteroids and antihistamines) are aimed at treating different allergic symptoms. Although they are highly effective, numerous factors, such as the dose and the route of administration, account for the efficacy of these treatments, and adverse effects are sometimes associated with a chronic use of these drugs [4]. Therefore, research into new anti-allergic therapy must be performed in order to make it effective from the prevention of allergic sensitization until the alleviation of allergy symptoms. Recent studies have highlighted different nutritional interventions that can impact on allergic diseases [5]. Dietary polyphenols have been found among these emerging nutraceuticals [6].

Flavonoids are products of the secondary metabolism of plants that are regularly ingested in small quantities in many edible plants. Chemically, they have a polyphenolic structure showing antioxidant activities. These properties have aroused an increasing interest in assessing their possible beneficial role in the prevention of various diseases, as evidenced by the large number of studies focused on the effect of flavonoids on health over the last decade [7], [8]. Considering the role of flavonoids in the immune system, most studies are performed in vitro, and those reports focusing on acquired immune response suggest that flavonoids produce an inhibitory effect on lymphocyte activation [9], [10], [11]. These studies show that flavonoids can affect both early and late phases of the immune response, including Th1 and Th2 effector responses, although a skewed effect of flavonoids favouring or inhibiting Th1 or Th2 responses has not been clearly established. Most preclinical studies on flavonoids in the acquired immune response use an antigen sensitization model followed by a challenge through different routes, searching to provoke a harmful immune response. Different types of flavonoids show the potential to suppress these damaging responses [12], [13], [14].

Cocoa is a rich source of polyphenols, particularly flavonoids such as (−)-epicatechin and (+)-catechin as well as procyanidins, the polymers derived from these monomers [15]. Previous studies demonstrated that a cocoa-enriched diet in rats was able to modify the composition and functionality of several lymphoid tissues [16], [17], [18], [19], decreasing serum IgG, IgM and IgA concentrations [16]. In addition, a cocoa diet in rats immunized with ovalbumin (OVA) attenuated anti-OVA IgG1 (the main isotype associated with the Th2 immune response in rats), IgG2a, IgG2c and IgM concentrations but led to higher amounts of anti-OVA IgG2b (the isotype linked to the Th1 response) [18]. Similarly, a cocoa diet was able to attenuate the specific antibody response in a rat model of chronic inflammation [19].

In light of this background which demonstrates the modulatory effect of cocoa on the immune system, the aim of this study was to ascertain whether a cocoa-enriched diet could also attenuate the synthesis of IgE in a rat allergy model.

Section snippets

Chemicals

The Natural Forastero cocoa (Nutrexpa, Barcelona, Spain) used in this study presented a total polyphenol content of about 22 mg/g with 2.2 mg/g (−)-epicatechin, 0.74 mg/g (+)-catechin and 1.7 mg/g procyanidin B2. Ovalbumin (OVA, grade V), albumin from bovine serum (BSA), gelatine, peroxidase-conjugated extravidin, o-phenylenediamine (OPD), and toxin from Bordetella pertussis (tBP) came from Sigma–Aldrich (Madrid, Spain). Imject® alum was obtained from Pierce (Rockford, IL, USA). Purified rat IgE,

Body weight

At the beginning of the study rats weighed 44.75 ± 6.79 g (mean ± S.E.M.). Body weight was monitored throughout the study and its time course was similar between both groups. At the end of the study, body weight was 99.31 ± 24.17 g [64.3–123.8 g] and 107.91 ± 15.19 g [90.4–135.3 g] in the reference and cocoa groups, respectively.

Serum anti-OVA IgG1, IgG2a and IgG2b antibodies

The serum concentrations of specific anti-OVA antibodies belonging to the IgG1, IgG2a and IgG2b isotypes are summarized in Fig. 1. Three weeks after OVA injection, the reference

Discussion

This study demonstrates that a diet containing 10% cocoa is able, in young rats, to prevent the synthesis of antibodies involved in allergic reaction. This result suggests that cocoa could be used as a nutraceutical in allergic diseases.

Previous studies demonstrated that cocoa diets attenuated antibody synthesis in Wistar rats after immunization [18], [19]. These results prompted us to ascertain what happens in an allergy model. In this study we induced the IgE synthesis by injecting Bordetella

Conclusion

In conclusion, a cocoa-enriched diet in young rats produces an immunomodulatory effect that prevents anti-allergen IgE synthesis and other Th2-associated antibodies. This diet also reduces TNF-α secretion, which can play a role in allergic inflammation. All these results suggest a potential role for cocoa flavonoids in the prevention or treatment of allergic diseases.

Acknowledgements

This study was supported by a grant from the Spanish Ministry of Science and Innovation (AGL2008-02790). The authors declare they have no conflicting interests. The authors wish to thank Nutrexpa S.L. for providing cocoa. The authors would also like to thank Alba Garcia-Just for her technical support.

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