Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Int Arch Allergy Immunol 2009;150:133–143 DOI: 10.1159/000218116 Effects of Live and Inactivated VSL#3 Probiotic Preparations in the Modulation of in vitro and in vivo Allergen-Induced Th2 Responses Giorgia Mastrangeli a Silvia Corinti a Cinzia Butteroni a Claudia Afferni a Angela Bonura b Monica Boirivant a Paolo Colombo b Gabriella Di Felice a a Department of Infectious, Parasitic and Immune-Mediated Diseases, Istituto Superiore di Sanità, Rome, b Istituto di Biomedicina ed Immunologia Molecolare ‘Alberto Monroy’, Consiglio Nazionale delle Ricerche, Palermo, Italy induced a significant reduction of serum specific IgG1. At lung level, VSL#3 pre-treatment remarkably reduced IL-13 and IL-4 mRNA expression and increased IL-10 expression. Conclusions: The VSL#3 preparations have not only the ca- pacity to bias primary immune responses towards a Treg/ Th0-type profile, but also to modify in the same way the functional characteristics of established in vitro Th2 respons- es. In vivo studies on a mouse model of Par j 1 sensitization indicate that the prophylactic intranasal treatment with pro- biotic bacteria is able to modulate the development of Th2- biased responses. Copyright © 2009 S. Karger AG, Basel Introduction An allergy can be considered as an inappropriate im- mune response to environmental factors, and is charac- terized by a tipping of the Th1/Th2 balance towards a pronounced Th2 profile [1] with induction of IgE synthe- sis and recruitment of eosinophils. IgE and eosinophils are the 2 factors that mediate most of the clinical symp- toms of allergy. Allergic sensitization of the airways with common aeroallergens is associated with the develop- ment of asthma and allergic rhinitis and affects 15–30% of the European population [2] . Non-allergic individuals Key Words Inhalant allergy  Probiotics  Recombinant allergens  Mouse models  Th2 immune responses  Immune regulation Abstract Background: The immunological mechanisms responsible for the immunomodulatory and anti-allergic effects of pro- biotic bacteria are still poorly defined. The combined effects of mixtures of different species of probiotic bacteria have been explored only in part. The present study describes the immunomodulatory activity of the VSL#3 probiotic prepara- tion in in vitro and in vivo systems. Methods: The activation and cytokine production by in vitro probiotic-stimulated bone-marrow dendritic cells (BM-DCs) and spleen cells iso- lated from naïve or Par j 1-sensitized mice were investigated. Mice were intranasally administered a sonicate preparation of VSL#3 before immunization with rPar j 1. Serum antibody levels and cytokine expression in the lung were determined. Results: Both live and sonicated VSL#3 preparations induced maturation and cytokine production by BM-DCs. Cytokine production by spleen cells from naïve or Par j 1-sensitized mice was modulated by the probiotic preparations towards a Treg/Th0 profile, characterized by increased IL-10 and IFN-  production. In vivo prophylactic treatment with VSL#3 Received: November 12, 2008 Accepted after revision: January 28, 2009 Published online: May 11, 2009 Correspondence to: Dr. Gabriella Di Felice Department of Infectious, Parasitic and Immune-Mediated Diseases Istituto Superiore di Sanità, Viale Regina Elena 299 IT–00161 Rome (Italy) Tel. +39 06 4990 2871, Fax +39 06 4938 7115, E-Mail difelice@iss.it © 2009 S. Karger AG, Basel 1018–2438/09/1502–0133$26.00/0 Accessible online at: www.karger.com/iaa