ABSTRACT
Allergen-specific immunotherapy (SIT) is an effective form of treatment for allergic diseases caused by inhalant allergens (e.g., pollen, mites, animal dander) and insect venom. Despite being initially described at the turn of the 20th 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 sensitization against new allergens (1,2). The treatment consists of administering increasing doses of natural allergen preparations on a regular basis, and the beneficial effects for the patient depend on the amount of allergen used. Typically, between 5 and 20 mg of the major allergen is required in each monthly maintenance injection to achieve optimal clinical efficacy. Because treatment involves injecting allergens into a sensitized individual, the occurrence of typical allergic symptoms, both local and systemic reactions, is not unexpected, with risks increasing with the concentration of allergen administered per treatment. Several immunological pathways seem to be involved in the clinical improvement achieved by the common SIT schedules (3,4). These mechanisms include (i) increase in allergen-specific IgG antibodies, in particular IgG4, which is believed to exert its effect by neutralizing allergen and blocking IgE-facilitated allergen presentation to T cells (5); (ii) generation of IgE modulating CD8þ T cells (6); (iii) reduction in the number of mast cells and eosinophils and the release of mediators by these cells (7,8); and (iv) modulation of allergen-specific T cells by shifting the response from a Th2 to Th1 cytokine pattern. The latter results in a decrease of IL-4 and IL-5 production accompanied by an increase of IFN-g (immune deviation) (9,10). Moreover, the induction of an anergic state in peripheral T cells (immunologic tolerance) has been reported. Tolerance may be mediated by IL-10 and has been characterized by suppressed proliferative and cytokine responses against major allergens (11).
