Intravenous or intranasal administration of gliadin is able to down-regulate the specific immune response in mice

The mucosal lesion in coeliac disease (CD) represents an immunologically me diated injury triggered by gliadin and is restricted by a particular assort ment of major histocompatibility complex (MHC) class IT genes. Therefore, i mmunomodulatory strategies to tolerize gliadin-specific, class II-restricte d T-cell responses could represent an alternative to current treatments of CD, which are based on a gluten-free diet. In this study, BALB/c mice deriv ed from a gluten-free diet colony were tolerized by either intranasal (i.n. ) or intravenous (i.v.) administration of single or multiple doses of gliad in. While a single dose failed to induce tolerance, a significant decrease in gliadin-specific T-cell proliferation was detected (P<0.001) after multi ple i.n. or i.v. administrations. No significant difference in antibody tit re was detected for antigen-specific immunoglobulin G (IgG) or the IgG(1) s ubclass, but a lower IgG(2a)-specific titre was observed. Both interferon-g amma (IFN-gamma) and interleukin (IL)-2 expression, measured by enzyme-link ed immunosorbent assay (ELISA) and reverse transcription-polymerase chain r eaction (RT-PCR), were reduced on antigen administration, both i.v. and i.n . Neither regimen showed a regulatory effect on IL-4 production. As T helpe r 1 (Th1) cytokines seem to be important in the pathogenesis of CD, our dat a therefore highlight the potential of i.n, and i.v. routes for the design of useful immunomodulatory strategies for CD.