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Effect of Theobroma cacao flavonoids on immune activation of a lymphoid cell line

Published online by Cambridge University Press:  08 March 2007

Emma Ramiro
Affiliation:
Department of Physiology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08 028, Barcelona, Spain
Àngels Franch
Affiliation:
Department of Physiology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08 028, Barcelona, Spain
Cristina Castellote
Affiliation:
Department of Physiology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08 028, Barcelona, Spain
Cristina Andrés-Lacueva
Affiliation:
Department of Nutrition and Food Science, Faculty of Pharmacy, University of Barcelona, Spain
Maria Izquierdo-Pulido
Affiliation:
Department of Nutrition and Food Science, Faculty of Pharmacy, University of Barcelona, Spain
Margarida Castell*
Affiliation:
Department of Physiology, Faculty of Pharmacy, University of Barcelona, Av. Joan XXIII s/n, 08 028, Barcelona, Spain
*
*Corresponding author: Dr Margarida Castell, fax +34 93 403 59 01, email margaridacastell@ub.edu
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Abstract

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We analysed the effect of (−)-epicatechin and cocoa extract on the activation of a lymphoid cell line. Particularly the expression of IL-2 receptor α (IL-2Rα or CD25) and, the secretion of IL-2 and IL-4 were established after flavonoid treatment. Two media culture conditions (1 and 10 % of fetal calf serum supplementation) and the different moments of flavonoid addition (simultaneously or 2 h before cell-activation) were compared. IL-2Rα (CD25) expression on activated cells was significantly reduced by epicatechin and cocoa extract in a dose-dependent manner, achieving the highest inhibition of about 50 % when flavonoids were added 2 h before stimulation. IL-2 secretion was also inhibited by the presence of both epicatechin and cocoa extract, displaying 60 and 75 % of inhibition, respectively. Cocoa flavonoids were also able to enhance 3–4·5-fold IL-4 release. In summary, cocoa extract down-modulated T lymphocyte activation and therefore the acquired immune response. This fact could be important in some states of the immune system hyperactivity such as autoimmune or chronic inflammatory diseases.

Type
Research Article
Copyright
Copyright © The Nutrition Society 2005

References

Alileche, A, Goldman, CK & Waldman, TA (2001) Differential effects of IL-2 and IL-15 on expression of IL-2 receptor α. Biochem Biophys Res Commun 285, 13021308.CrossRefGoogle ScholarPubMed
Allen, JB, Wong, HL, Costa, GL, Bienkowski, MJ & Wahl, SM (1993) Suppression of monocyte function and differential regulation of IL-1 and Il-1ra by IL-4 contribute to resolution of experimental arthritis. J Immunol 151, 43444351.CrossRefGoogle ScholarPubMed
Andrés-Lacueva, C, Lamuela-Raventós, RM, Jáuregui, O, Casals, I, Izquierdo-Pulido, M & Permanyer, J (2000) An LC method for the analysis of cocoa phenolics. LC-GC Europe 12, 902905.Google Scholar
Arts, ICW, Hollman, PCH & Kromhout, D (1999) Chocolate as a source of tea flavonoids. Lancet 354, 488.CrossRefGoogle ScholarPubMed
Atluru, D, Jackson, TM & Atluru, S (1991) Genistein, a selective protein tyrosine kinase inhibitor, inhibits interleukin-2 and leukotriene B4 production from human mononuclear cells. Clin Immunol Immunopathol 59, 379387.CrossRefGoogle ScholarPubMed
Baba, S, Osakabe, N, Yasuba, A, Natsume, M, Takizawa, T, Nakamura, T & Terao, J (2000) Bioavailability of (2)-epicatechin upon intake of chocolate and cocoa in human volunteers. Free Radic Res 33, 635641.CrossRefGoogle Scholar
Bell, JR, Donovan, JL, Wong, R, Waterhouse, AL, German, JB, Walzem, RL & Kasim-Karakas, SE (2000) (+)-Catechin in human plasma after ingestion of a single serving of reconstituted red wine. Am J Clin Nutr 71, 103108.CrossRefGoogle ScholarPubMed
Cerqueira, FCordeiro-da-Silva, AAraujo, N, Cidade, H, Kijjoa, A & Nascimento, MS (2003) Inhibition of lymphocyte proliferation by prenylated flavones: artelastin as a potent inhibitor. Life Sci 73, 23212334.CrossRefGoogle ScholarPubMed
Cho, KJ, Yun, CH, Packer, L & Chung, AS (2001) Inhibition mechanisms of biflavonoids extracted from the bark of Pinus maritima on the expression of proinflamatory cytokines. Ann N Y Acad Sci 928, 141156.CrossRefGoogle Scholar
Constant, SL & Bottomly, K (1997) Induction of Th1 and Th2 CD4 + responses: the alternative approaches. Annu Rev Immunol 15, 297322.CrossRefGoogle ScholarPubMed
Depper, JM, Leonard, WJ, Drogula, C, Kronke, M, Waldman, TA & Greene, WC (1985) Interleukin 2 (IL-2) augments transcription of the IL-2 receptor gene. Proc Natl Acad Sci U S A 82, 42304234.CrossRefGoogle ScholarPubMed
Dillinger, TL, Barriga, PEscárcega, SJimenez, MSalazar, Lowe D & Grivett, LE (2000) Food for goods: cure for humanity? A cultural history of the medicinal and ritual use of chocolate. J Nutr 130, 2057S2072S.CrossRefGoogle Scholar
Dornand, J, Bouaboulia, MDupuy, d'angeac A, Favero, J, Shire, D & Casellas, P (1992) Contrasting effects of the protein kinase C inhibitor staurosporine on the interleukin-1 and phorbol ester activation pathways in the EL4-6.1 thymoma cell line. J Cell Physiol 151, 7180.CrossRefGoogle ScholarPubMed
Field, CJ (2000) Use of T cell function to determine the effect of physiologically active food components. Am J Clin Nutr 71, 170S175S.CrossRefGoogle ScholarPubMed
Ghoreschi, K, Thomas, P, Breit, S, et al. (2003) Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease. Nat Med 9, 4046.CrossRefGoogle ScholarPubMed
Greene, WC & Leonard, WJ (1986) The human interleukin-2 receptor. Annu Rev Immunol 4, 6996.CrossRefGoogle ScholarPubMed
Hammerstone, JF, Lazarus, S, Mitchell, A, Rucker, R & Schmitz, HH (1999) Identification of procyanidins in cocoa (Theobroma cacao) and chocolate using high-performance liquid chromatography/mass spectrometry. J Agric Food Chem 47, 490496.CrossRefGoogle ScholarPubMed
Hatakeyama, M & Taniguchi, T (1990) Interleukin-2. In Handbook of Experimental Pharmacology, vol. 95/I; Peptide Growth Factors and their Receptors, pp. 523540. [Spron, MB and Roberts, AB, editors] Berlin: Heidelberg: Springer-Verlag.CrossRefGoogle Scholar
Holt, RR, Lazarus, SA, Sullards, MC, Zhu, QY, Schramm, DD, Hammerstone, JF, Fraga, CG, Schmitz, HH & Keen, CL (2002) Procyanidin dimer B2 (epicatechin-(4β-8)-epicatechin) in human plasma after the consumption of a flavanol-rich cocoa. Am J Clin Nutr 76, 798804.CrossRefGoogle Scholar
Hurst, WJ, Tarka, SM, Powis, TG, Valdez, F & Hester, TR (2002) Cacao usage by earliest Maya civilization. Nature 418, 289.CrossRefGoogle ScholarPubMed
Johnson, VJ, He, Q, Osuchowski, MF & Sharma, RP (2003) Physiological responses of a natural antioxidant flavonoid mixture, silymarin, in BALB/c mice: III. Silymarin inhibits T-lymphocyte function at low doses but stimulates inflammatory processes at high doses. Planta Med 69, 4449.CrossRefGoogle ScholarPubMed
Kelly, DS & Bendich, A (1996) Essential nutrients and immunologic functions. Am J Clin Nutr 63, 994S996S.CrossRefGoogle Scholar
Kris-Etherton, PM & Keen, CL (2002) Evidence that the antioxidant flavonoids in tea and cocoa are beneficial for cardiovascular health. Curr Opin Lipidol 13, 4149.CrossRefGoogle ScholarPubMed
Kubena, KS & McMurray, DN (1996) Nutrition and the immune system: a review of nutrient-nutrient interactions. J Am Diet Assoc 96, 11561164.CrossRefGoogle ScholarPubMed
Kunishiro, K, Tai, A & Yamamoto, I (2001) Effects of rooibos tea extract on antigen-specific antibody production and cytokine generation in vitro and in vivo. Biosci Biotechnol Biochem 65, 21372145.CrossRefGoogle ScholarPubMed
Lamuela, RM, Andrés-Lacueva, C, Permanyer, J & Izquierdo-Pulido, M (2001) More antioxidants in cocoa. J Nutr 131, 834.CrossRefGoogle Scholar
Mackenzie, GG, Carrasquedo, F, Delfino, JM, Keen, CL, Fraga, CG & Oteiza, PI (2004) Epicatechin, catechin, and dimeric procyanidins inhibit PMA-induced NF-κB activation at multiple steps in Jurkat T cells. FASEB J 18, 167169.CrossRefGoogle ScholarPubMed
Manach, C, Scalbert, A, Morand, C, Rémésy, CJiménez, L (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79, 727747.CrossRefGoogle ScholarPubMed
Mao, TK, Powell, JJ, Van de Water, J, Keen, CL, Schmitz, HH & Gershwin, ME (1999) The influence of cocoa procyanidins on the transcription of interleukin-2 in peripheral blood mononuclear cells. Int J Immunotherapy 15, 2329.Google Scholar
Mao, TK, Powell, JJ, Van de Water, J, Keen, CL, Schmitz, HH, Hammerstone, JF & Gershwin, ME (2000a) The effect of cocoa procyanidins on the transcription and secretion of interleukin 1β in peripheral blood mononuclear cells. Life Sci 66, 13771386.CrossRefGoogle Scholar
Mao, TK, Powell, JJ, Van de Water, J, Keen, CL, Schmitz, HH & Gershwin, ME (2000b) Effect of cocoa procyanidins on the secretion of interleukin-4 in peripheral blood mononuclear cells. J Med Food 3, 107114.CrossRefGoogle Scholar
Mao, TK, Van de Water, J, Keen, CL, Schmitz, HH & Gershwin, ME (2000c) Cocoa procyanidins and human cytokine transcription and secretion. J Nutr 130, 2093S2099S.CrossRefGoogle ScholarPubMed
Mao, TK, Van de Water, J, Keen, CL, Schmitz, HH & Gershwin, ME (2002a) Modulation of TNF-α secretion in peripheral blood mononuclear cells by cocoa flavanols and procyanidins. Dev Immunol 9, 135141.CrossRefGoogle ScholarPubMed
Mao, TK, Van de Water, J, Keen, CL, Schmitz, HH & Gershwin, ME (2002b) Effect of cocoa flavanols and their related oligomers on the secretion of interleukin-5 in peripheral blood mononuclear cells. J Med Food 5, 1722.CrossRefGoogle ScholarPubMed
Mao, TK, Van de Water, J, Keen, CL, Schmitz, HH & Gershwin, ME (2003) Cocoa flavonols and procyanidins promote transforming growth factor-β 1 homeostasis in peripheral blood mononuclear cells. Exp Biol Med 228, 9399.CrossRefGoogle ScholarPubMed
Meydani, SN, Meydani, M, Blumberg, J, Leka, LS, Pedrosa, M, Diamond, R & Schaefer, EJ (1998) Assessment of the safety of supplementation with different amounts of vitamin E in healthy older adults. Am J Clin Nutr 68, 311318.CrossRefGoogle ScholarPubMed
Nelson, BH & Willerford, DM (1998) Biology of the interleukin-2 receptor. Adv Immunol 70, 181.CrossRefGoogle Scholar
Noé, V, Peñuelas, S, Lamuela-Raventós, RM, Permanyer, J, Ciudad, CJ & Izquierdo-Pulido, M (2004) Epicatechin and cocoa polyphenolic extract modulate gene expression in human Caco-2-cells. J Nutr 134, 25092516.CrossRefGoogle ScholarPubMed
Okamoto, I, Iwaki, KKoya-Miyata, STanimoto, T, Kohno, K, Ikeda, M & Kurimoto, M (2002) The flavonoid kaempferol suppresses the graft-versus-host reaction by inhibiting type 1 cytokine production and CD8+T cell engraftment. Clin Immunol 103, 132144.CrossRefGoogle ScholarPubMed
Pearson, DA, Paglieroni, TG, Rein, D, Wun, T, Schramm, DD, Wang, J, Holt, RR, Gosselin, R, Schmitz, HH & Keen, CL (2002) The effects of flavanol-rich cocoa and aspirin on ex vivo platelet function. Thromb Res 106, 191197.CrossRefGoogle ScholarPubMed
Pietta, PG (2000) Flavonoids as antioxidants. J Nat Prod 63, 10351042.CrossRefGoogle ScholarPubMed
Powell, JD, Ragheb, JA, Kitagawa-Sakakida, S & Schwartz, RH (1998) Molecular regulation of interleukin-2 expression by CD28 co-stimulation and anergy. Immunol Rev 165, 287300.CrossRefGoogle ScholarPubMed
Proust, JJ, Shaper, NL, Buchholz, MA & Nordin, AA (1991) T cell activation in the absence of interleukin 2 (IL-2) results in the induction of high affinity IL-2 receptor unable to transmit a proliferative signal. Eur J Immunol 21, 335341.CrossRefGoogle ScholarPubMed
Richelle, M, Tavazzi, I, Ensien, M & Offord, E (1999) Plasma kinetics in man of epicatechin from black chocolate. Eur J Clin Nutr 53, 2226.CrossRefGoogle ScholarPubMed
Rios, LY, Bennett, RN, Lazarus, SA, Rémésy, CScalbert, A & Williamson, G (2002) Cocoa procyanidins are stable during gastric transit in humans. Am J Clin 76, 11061110.CrossRefGoogle ScholarPubMed
Rios, LY, Gonthier, MP, Rémesy, C, Mila, I, Lapierre, C, Lazarus, SA, Williamson, G & Scalbert, A (2003) Chocolate intake increases urinary excretion of polyphenol-derived phenolic acids in healthy human subjects. Am J Clin Nutr 77, 912918.CrossRefGoogle ScholarPubMed
Sanbongi, C, Suzuki, N & Tsuyoshi, S (1997) Polyphenols in chocolate, which have antioxidant activity, modulate immune functions in humans in vitro. Cell Immunol 177, 129136.CrossRefGoogle ScholarPubMed
Sánchez-Rabaneda, F, Jáuregui, O, Casals, I, Andrés-Lacueva, C, Izquierdo-Pulido, M & Lamuela-Raventós, RM (2003) Liquid chromatographic/electrospray ionization tandem mass spectrometric study of the phenolic composition of cocoa (Theobroma cacao). J Mass Spectrom 38, 3542.CrossRefGoogle ScholarPubMed
Schramm, DD, Wang, JF, Holt, RR, Enunsa, JL, Gonsalves, JL, Lazarus, SA, Schmitz, HH, German, JB & Keen, CL (2001) Chocolate procyanidins decrease leukotriene-prostacyclin ratio in humans and human aortic endothelial cells. Am J Clin Nutr 73, 3640.CrossRefGoogle ScholarPubMed
Smith, KA & Cantrell, DA (1985) Interleukin 2 regulates its own receptors. Proc Natl Acad Sci U S A 82, 864868.CrossRefGoogle ScholarPubMed
Spanish Department of Agriculture, Fishery and Food (2002). La alimentación en España 2002. Madrid: Spanish Department of Agriculture, Fishery and Food.Google Scholar
Steinberg, FM, Bearden, M & Keen, CL (2003) Cocoa and chocolate flavonoids: implications for cardiovascular health. J Am Diet Assoc 103, 215223.CrossRefGoogle ScholarPubMed
Stoeck, M, Lees, R, Szamel, M, Pantaleo, GMcDonald, HR (1989) Comparison of phorbol-12-myristate-13-acetate and dioctanoyl-sn-glycerol in the activation of EL4/6·1 thymoma cells. J Cell Physiol 138, 541547.CrossRefGoogle ScholarPubMed
Swain, T & Hillis, WE (1969) The total phenolic constituents of Prunus domestica. J Sci Food Agric 46, 42924296.Google Scholar
Vinson, JA, Proch, J & Zubick, L (1999) Phenol antioxidant quantity and quality in foods: cocoa, dark chocolate and milk chocolate. J Agric Food Chem 47, 48214824.CrossRefGoogle ScholarPubMed
Waldmann, TA, Goldman, CK, Robb, RJ, Depper, JM, Leonard, WJ, Sharrow, SO, Bongiovanni, K, Korsmeyer, SJ & Greene, WC (1984) Expression of interleukin 2 receptor on activated human B cells. J Exp Med 160, 14501466.CrossRefGoogle ScholarPubMed
Waterhouse, AL, Shirley, JR & Donovan, JL (1996) Antioxidants in chocolate (letter). Lancet 348, 834.CrossRefGoogle Scholar
Weisburger, JH (2001) Chemopreventive effects of cocoa polyphenols on chronic diseases. Exp Biol Med 226, 891897.CrossRefGoogle ScholarPubMed