Authors: F Calcinaro S Dionisi M Marinaro P Candeloro V Bonato S Marzotti R B Corneli E Ferretti A Gulino F Grasso C De Simone U Di Mario A Falorni M Boirivant F Dotta
Publish Date: 2005/06/29
Volume: 48, Issue: 8, Pages: 1565-1575
Abstract
Recent observations suggest the involvement of the gastrointestinal tract in the pathogenesis of islet autoimmunity Thus the modulation of gutassociated lymphoid tissue may represent a means to affect the natural history of the disease Oral administration of probiotic bacteria can modulate local and systemic immune responses consequently we investigated the effects of oral administration of the probiotic compound VSL3 on the occurrence of diabetes in nonobese diabetic NOD miceVSL3 was administered to female NOD mice three times a week starting from 4 weeks of age A control group received PBS Whole blood glucose was measured twice a week IFNγ and IL10 production/expression was evaluated by ELISA in culture supernatants of mononuclear cells isolated from Peyer’s patches and the spleen and by realtime PCR in the pancreas Insulitis was characterised by immunohistochemistry and histomorphometric studiesEarly oral administration of VSL3 prevented diabetes development in NOD mice Protected mice showed reduced insulitis and a decreased rate of beta cell destruction Prevention was associated with an increased production of IL10 from Peyer’s patches and the spleen and with increased IL10 expression in the pancreas where IL10positive isletinfiltrating mononuclear cells were detected The protective effect of VSL3 was transferable to irradiated mice receiving diabetogenic cells and splenocytes from VSL3treated miceOrally administered VSL3 prevents autoimmune diabetes and induces immunomodulation by a reduction in insulitis severity Our results provide a sound rationale for future clinical trials of the primary prevention of type 1 diabetes by oral VSL3 administration
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