Background: Previous studies suggest that administration of probiotics in vitro can stimulate regulatory and Th1 immune responses. We studied both the in vitro immunological effects of probiotics and the ex vivo immunological effects after oral administration of probiotics in children with food allergy, a Th2-mediated disease. Methods: Thirteen children were enrolled. Probiotics (n = 7) or placebo (n = 6) were orally administered during 3 months. At baseline and after 1 and 3 months, peripheral blood mononuclear cells were stimulated with crude peanut extract, anti-CD3, or anti-CD40 and IL-4 in the presence (in vitro response) or absence (ex vivo response) of probiotics. The proliferation and production of IFN-γ, IL-5, IL-13, IL-10, TNF-α, IL-6 and IgE were analyzed. Sensitization to peanut, cow’s milk and hen’s egg was determined before and after treatment. Results: The in vitro addition of probiotics to peripheral blood mononuclear cell cultures resulted in enhanced proliferation and production of IFN-γ, IL-10 and TNF-α. After oral treatment, proliferation in the presence of probiotics increased, whereas in vitro IgE production decreased in the probiotics group compared to baseline. The ex vivo production of IL-10, TNF-α and IL-6 tended to decrease. Th1 and Th2 cytokines were not altered. Sensitization remained unchanged. Conclusion: Probiotics enhanced the production of Th1 and regulatory cytokines in vitro. Oral administration of probiotics resulted in a slightly decreased ex vivo production of IL-10, TNF-α and IL-6. This indicates that probiotics have a different potential to modulate the immune response in vitro versus ex vivo.

Keywords:
Probiotics, T cell, Cytokine, Food allergy
1.
The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee: Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema: ISAAC. Lancet 1998;351:1225–1232.
2.
Martinez FD, Holt PG: Role of microbial burden in aetiology of allergy and asthma. Lancet 1999;354(suppl 2):SII12–SII15.
3.
Björkstén B, Naaber P, Sepp E, Mikelsaar M: The intestinal microflora in allergic Estonian and Swedish 2-year-old children. Clin Exp Allergy 1999;29:342–346.
4.
Björkstén B, Sepp E, Julge K, Voor T, Mikelsaar M: Allergy development and the intestinal microflora during the first year of life. J Allergy Clin Immunol 2001;108:516–520.
5.
Marteau PR: Probiotics in clinical conditions. Clin Rev Allergy Immunol 2002;22:255–273.
6.
Cross ML, Gill HS: Can immunoregulatory lactic acid bacteria be used as dietary supplements to limit allergies? Int Arch Allergy Immunol 2001;125:112–119.
7.
Karlsson H, Larsson P, Wold AE, Rudin A: Pattern of cytokine responses to Gram-positive and Gram-negative commensal bacteria is profoundly changed when monocytes differentiate into dendritic cells. Infect Immun 2004;72:2671–2678.
8.
Mohamadzadeh M, Olson S, Kalina WV, Ruthel G, Demmin GL, Warfield KL, et al: Lactobacilli activate human dendritic cells that skew T cells toward T helper 1 polarization. Proc Natl Acad Sci USA 2005;102:2880–2885.
9.
Majamaa H, Isolauri E: Probiotics: a novel approach in the management of food allergy. J Allergy Clin Immunol 1997;99:179–185.
10.
Viljanen M, Savilahti E, Haahtela T, Juntunen-Backman K, Korpela R, Poussa T, et al: Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial. Allergy 2005;60:494–500.
11.
Schade RP, Van Ieperen-Van Dijk AG, Van Reijsen FC, Versluis C, Kimpen JL, Knol EF, et al: Differences in antigen-specific T-cell responses between infants with atopic dermatitis with and without cow’s milk allergy: relevance of TH2 cytokines. J Allergy Clin Immunol 2000;106:1155–1162.
12.
Pessi T, Sutas Y, Hurme M, Isolauri E: Interleukin-10 generation in atopic children following oral Lactobacillus rhamnosus GG. Clin Exp Allergy 2000;30:1804–1808.
13.
Pohjavuori E, Viljanen M, Korpela R, Kuitunen M, Tiittanen M, Vaarala O, et al: Lactobacillus GG effect in increasing IFN-γ production in infants with cow’s milk allergy. J Allergy Clin Immunol 2004;114:131–136.
14.
Prescott SL, Dunstan JA, Hale J, Breckler L, Lehmann H, Weston S, et al: Clinical effects of probiotics are associated with increased interferon-γ responses in very young children with atopic dermatitis. Clin Exp Allergy 2005;35:1557–1564.
15.
Niers LE, Timmerman HM, Rijkers GT, van Bleek GM, van Uden NO, Knol EF, et al: Identification of strong interleukin-10 inducing lactic acid bacteria which down-regulate T helper type 2 cytokines. Clin Exp Allergy 2005;35:1481–1489.
16.
Yssel H, De Vries JE, Koken M, Van BW, Spits H: Serum-free medium for generation and propagation of functional human cytotoxic and helper T cell clones. J Immunol Methods 1984;72:219–227.
17.
Cross ML, Ganner A, Teilab D, Fray LM: Patterns of cytokine induction by Gram-positive and Gram-negative probiotic bacteria. FEMS Immunol Med Microbiol 2004;42:173–180.
18.
Rosenfeldt V, Benfeldt E, Nielsen SD, Michaelsen KF, Jeppesen DL, Valerius NH, et al: Effect of probiotic Lactobacillus strains in children with atopic dermatitis. J Allergy Clin Immunol 2003;111:389–395.
19.
Rosenfeldt V, Benfeldt E, Valerius NH, Paerregaard A, Michaelsen KF: Effect of probiotics on gastrointestinal symptoms and small intestinal permeability in children with atopic dermatitis. J Pediatr 2004;145:612–616.
20.
Eizaguirre I, Urkia NG, Asensio AB, Zubillaga I, Zubillaga P, Vidales C, et al: Probiotic supplementation reduces the risk of bacterial translocation in experimental short bowel syndrome. J Pediatr Surg 2002;37:699–702.
21.
Braat H, van den BJ, van Tol E, Hommes D, Peppelenbosch M, van Deventer S: Lactobacillus rhamnosus induces peripheral hyporesponsiveness in stimulated CD4+ T cells via modulation of dendritic cell function. Am J Clin Nutr 2004;80:1618–1625.
22.
Matricardi PM, Bonini S: High microbial turnover rate preventing atopy: a solution to inconsistencies impinging on the Hygiene hypothesis? Clin Exp Allergy 2000;30:1506–1510.
23.
Kalliomäki M, Salminen S, Arvilommi H, Kero P, Koskinen P, Isolauri E: Probiotics in primary prevention of atopic disease: a randomised placebo-controlled trial. Lancet 2001;357:1076–1079.
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2007
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