Allergen immunotherapy: the good, the bad, and the unknown.

demonstrated in several aspects, including the reduction of symptom scores, reduction of medication used, reduced response to allergen challenge, and improved quality of life in both children and adults [4]. The clinical benefits of allergen immunotherapy are accompanied by complex immunological changes. These include the generation of T regulatory cells producing inhibitory cytokines such as interleukin-10 and transforming growth factor-beta, an initial increase followed by decrease in specific immunoglobulin E levels, and a delayed increase in levels of allergen-specific IgG41 [6]. However, no consistent association was demonstrated for those immunological changes and the clinical response to treatment. The efficacy of allergen immunotherapy, which was initially demonstrated for grass pollen, was subsequently proven also for fungi, animal allergens, house dust mite, and cockroaches [4]. Furthermore, beyond the direct effect of allergen immunotherapy on the sensitivity to a particular allergen, there are additional long-term benefits with this form of therapy. First, the effect of allergen immunotherapy, on both clinical symptoms and medication use, might extend even after treatment is discontinued [7]. Second, the effect of allergen immunotherapy might extend beyond the particular allergen the patient is immunized for, thus preventing the development of new allergen sensitivities in mono-immunized patients [8]. Moreover, in allergic children with wheezing, allergen immunotherapy was demonstrated to prevent a subsequent development of asthma [9]. Still, despite a century of practice, many unanswered questions regarding allergen immunother-