• Immunotherapy;
  • Insect venom;
  • Interleukin-10;
  • Cytokine;
  • Allergy


The current study was carried out to elucidate the immunoregulatory changes induced by venom immunotherapy (VIT) in bee or wasp allergic subjects. All subjects included in this study had a history of severe systemic allergic reactions to stings of the respective insect as well as positive skin tests with the respective venom or venom-specific IgE in the sera. Parameters assessed in peripheral blood mononuclear cells (PBMC) before and after initiation of VIT (rush therapy reaching a maintenance dose of 100 μg venom injected subcutaneously within 1 week) were expression of CD3, CD4, CD8, CD45RA, CD45R0, interleukin (IL)-2 receptor (R)α, IL-4R, IL-12R, FcσRII, CD40, and CD40 ligand (CD40L), cells producing interferon (IFN)-γ and IL-10 after stimulation with phorbol 12-myristate 13-acetate + ionomycin in the presence of monensin measured by flow cytometry; secretion of IFN-γ, IL-4, and IL-10 measured by ELISA (IFN-γ and IL-10 were additionally measured by PCR), and proliferation after stimulation with the respective venom. Significant decreases were observed after VIT for proliferative response to venom and venom + IL-4, IL-4 secretion, FcσRII, CD40, and CD40L expression. Significant increases were observed after VIT for IFN-γ concerning the amount secreted and the number of producing cells, and IL-10. IL-10 was mainly produced by CD4+ cells that were negative for IFN-γ, but some double-positive (IL-10 and IFN-γ) cells were always detected. Addition of blocking anti-IL-10 antibodies, but not isotype control antibodies, prevented down-regulation of proliferation (but not IL-4 secretion) and further enhanced IFN-γ secretion after VIT. These data indicate that in insect venom allergic subjects, VIT not only induces a rapid shift in cytokine expression from Th2 to Th1 cytokines, but also leads to induction of the immunosuppressive cytokine IL-10, which may be important for the limitation of potentially harmful allergen-specific Th1 responses. The described changes in cytokine expression may be responsible for subsequent increases in allergen-specific IgG and decreases in IgE production, as well as suppressive activity observed in earlier studies.