title: Insect venom immunotherapy induces interleukin-10 production and a Th2-to-Th1 shift, and changes surface marker expression in venom-allergic subjects.
abstract: 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 micrograms venom injected subcutaneously within 1 week) were expression of CD3, CD4, CD8, CD45RA, CD45RO, interleukin (IL)-2 receptor (R) alpha, IL-4R, IL-12R, Fc epsilon RII, CD40, and CD40 ligand (CD40L), cells producing interferon (IFN)-gamma and IL-10 after stimulation with phorbol 12-myristate 13-acetate + ionomycin in the presence of monensin measured by flow cytometry; secretion of IFN-gamma, IL-4, and IL-10 measured by ELISA (IFN-gamma 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, Fc epsilon RII, CD40, and CD40L expression. Significant increases were observed after VIT for IFN-gamma 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-gamma, but some double-positive (IL-10 and IFN-gamma) 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-gamma 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.
authors.affiliation: Department of Dermatology, University of Mainz, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Bellinghausen
authors.forename: G
authors.initials: G
authors.lastname: Metz
authors.forename: A H
authors.initials: AH
authors.lastname: Enk
authors.forename: S
authors.initials: S
authors.lastname: Christmann
authors.forename: J
authors.initials: J
authors.lastname: Knop
authors.forename: J
authors.initials: J
authors.lastname: Saloga
mesh_terms: D000485:Allergens / Q000494:pharmacology* / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D000954:Antigens, Surface / Q000096:biosynthesis*; D001514:Bee Venoms / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand; D003888:Desensitization, Immunologic / Q000379:methods; D015536:Down-Regulation / Q000276:immunology; D006801:Humans; D007299:Insect Bites and Stings / Q000276:immunology / Q000628:therapy*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008024:Ligands; D008213:Lymphocyte Activation / Q000187:drug effects; D018655:Lymphocyte Count; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D017455:Receptors, IgE / Q000096:biosynthesis; D018123:Receptors, Interleukin / Q000096:biosynthesis; D019948:Receptors, Interleukin-4; D016176:T-Lymphocyte Subsets / Q000166:cytology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D013997:Time Factors; D014862:Wasp Venoms / Q000276:immunology / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000485:Allergens; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000954:Antigens, Surface; D001514:Bee Venoms; D019013:CD40 Antigens; D008024:Ligands; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D017455:Receptors, IgE; D018123:Receptors, Interleukin; D019948:Receptors, Interleukin-4; D014862:Wasp Venoms; D016753:Interleukin-10; D023201:CD40 Ligand; D015847:Interleukin-4; D007371:Interferon-gamma