ABSTRACT
I. INTRODUCTION Allergen specific immunotherapy (SIT) is an effective fonn of treatment for allergic diseases caused by inhalant allergens (e.g., pollen, mites, animal dander) and insect venom. Despite being initially described at the tum of the twentieth century, SIT remains the only "curative" approach to atopic allergic disease. In addition to the ability to modulate existing disease, SIT is capable of modifying the natural course by preventing the worsening of symptoms (from rhinitis to asthma) and the onset of sensitization against new allergens (1,2). SIT consists of administering increasing doses of natural allergen preparations on a regular basis; the beneficial effects for the patient depend on the amount
of allergen given. Typically, between 5 and 20 Ilg of the major allergen is required in each monthly maintenance injection to achieve optimal clinical efficacy. Because SIT involves injecting allergens into a sensitized individual, the occurrence of typical allergic symptoms is frequent, with risks increasing with higher concentration of the allergen injected. Several immunological pathways are involved in the clinical improvement achieved by the usual SIT schedules (3,4): a rise in allergen-specific IgG antibodies, in particular IgG4, which exerts its effect by neutralizing allergen and blocking IgE-facilitated allergen presentation to T-cells (5); generation of antigen-specific CD8+ suppressor T-cells (6); a reduction in the number of mast cells and eosinophils, and diminished release of mediators (7,8); modulation of allergen-specific T-cells-a shift from the TH2 to the THI cytokine pattern with a decrease of IL-4 and IL-5 production accompanied by an increase of IFN-y (immune deviation) (9, 10). Moreover, the induction of an anergic state in peripheral T-cells (immunological tolerance) has been reported. The latter may be mediated by IL-IO and has been characterized by suppressed proliferative and cytokine responses against major allergens (II).
