title: [Theories on the mode of action of desensitization].
abstract: Specific immunotherapy (SIT) has been practised successfully for about 80 years. In classic immunotherapy, an allergen-extract is repeatedly injected subcutaneously in increasing doses. A large number of clinically controlled studies have proved the efficacy of this kind of immunotherapy, while its mode of action is not precisely known yet. A successful SIT leads to an impairment of allergic symptoms (symptom score), and a concordant decrease in drug use. Furthermore, a reduced reactivity in specific dermal, nasal and bronchial provocation tests is induced as well as a diminished unspecific reagibility in the affected tissues. Several studies showed reduced values for allergen-specific IgE (serum) that followed an initial increase. A reduced immigration of eosinophils was found, both after provocation with allergen and during the pollen season, as well as diminished values of markers for the activity of eosinophils, e.g. eosinophil cationic protein (ECP). Also, a reduced allergen-induced histamine-liberation from mast cells and basophils has been reported. The underlying mechanism for these effects of SIT might be a reorientation of the allergen-induced lymphokine-production to a dominant TH1-cytokine-profile. Because the relation between the quantity of IL-4 and its regulator IFN-gamma controls the extent of IgE-synthesis by B-cells, the reorientation leads to a diminished production of IgE. IFN-gamma inhibits the differentiation of TH2-cells; by this less TH2-cells are present to help B-cells to produce IgE-antibodies, and to induce the differentiation of mast cells and basophils as well as immigration, differentiation and activation of eosinophils. Thus, the positive effects of SIT can be explained by the reorientation T-cell lymphokine profile. The mechanism under discussion for explaining this reorientation include: 1) an increased differentiation of allergen-specific CD4+ precursor-cells or a reorientation of established TH2-cells to the production of IFN-gamma, 2) the differentiation of IFN-gamma-producing CD8+ T-cells and of T-cells with receptors for T-cell-antigenes of the gamma, delta-type; and 3) the induction of an energy in TH2-cells.
authors.affiliation: Hals-, Nasen-, Ohren-Universitätsklinik Mainz, Deutschland. klimek@hno.klinik.uni-mainz.de
authors.forename: L
authors.initials: L
authors.lastname: Klimek
authors.forename: A B
authors.initials: AB
authors.lastname: Reske-Kunz
authors.forename: J
authors.initials: J
authors.lastname: Saloga
mesh_terms: D000485:Allergens / Q000494:pharmacology / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002454:Cell Differentiation; D003888:Desensitization, Immunologic; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018448:Models, Immunological; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D012221:Rhinitis, Allergic, Perennial / Q000276:immunology / Q000628:therapy*; D016176:T-Lymphocyte Subsets / Q000378:metabolism*
chemical_list: D000485:Allergens; D016692:Receptors, Antigen, T-Cell, gamma-delta; D007371:Interferon-gamma
vernacular_title: Theorien zur Wirkweise der Hyposensibilisierung.