Specific immunotherapy prevents increased levels of allergen-specific IL-4-and IL-13-producing cells during pollen season

Background: Specific allergen immunotherapy (SIT) is effective for treatment of IgE-mediated diseases; however, the mechanisms of action still remain unclear. Earlier, we showed that IL-4 and IL-13 are produced in response to specific allergens. The aim of this study was to investigate whether these cytokine responses were affected by allergen SIT, and, furthermore, to evaluate the effect of SIT on allergen-specific IgE and IgG4 levels. Methods: Blood samples from pollen-sensitized individuals were collected before the pollen season (before treatment) and during the pollen season (after SIT or placebo treatment). Peripheral blood mononuclear cells were activated in vitro with allergens and the numbers of IL-4-, IL-13-, IL-10-, and IFN-gamma -producing cells were determined by ELISPOT. Serum levels of allergen-specific IgE and IgG4 were measured by RAST and ELISA, respectively. Results: The numbers of IL-4- and IL-13-producing cells were shown to be increased in the placebo group during the pollen season, an increment which was absent in patients receiving allergen SIT. We found an increase in allergen-specific IgG4 in the SIT-treated individuals, but not in the placebo group. Both groups displayed elevated specific IgE levels during the pollen season. Conclusions: Taken together, our data show a downregulation of IL-4- and IL-13-producing cells in peripheral blood after SIT, suggesting induction of nonresponsiveness/tolerance or a redistribution of these cells. Furthermore, we demonstrate that SIT acts on antibody production by increasing the specific IgG4 levels.