Allergen-specific immunotherapy for allergic rhinitis: a new insight into its clinical efficacy and mechanism

Immunotherapy has been used widely for allergic diseases for more than 90 years but, in the opinion of many physicians, it is still a controversial form of treatment. The exact mechanism of action of immunotherapy remains to be determined. In the present study, we review the clinical efficacy and mechanism of action of immunotherapy for allergic rhinitis. Recent double-blind placebo-controlled studies have demonstrated the clinical efficacy of immunotherapy for allergic rhinitis. This therapeutic method has several advantages over conventional pharmacological treatment. Immunotherapy is inferior to pharmacological treatment in the short term, but in the long term it is substantially superior with respect to clinical efficacy. Immunotherapy has the potential permanently to alleviate the abnormal immunological responses of allergic rhinitis and to cure the nasal symptoms in the long term, even after discontinuation of injections. In addition, immunotherapy can prevent the onset of new sensitizations in allergic patients and may prevent the progression of rhinitis to asthma. It may therefore be possible for immunotherapy to alter the natural history of allergic sensitization and its clinical manifestation. These lines of clinical evidence could affect strategies of long-term therapy for allergic rhinitis. Modern molecular biological techniques have suggested that immunotherapy may affect allergen-induced TH responses or cytokine profiles, but there is no general agreement among investigators. However, IL-5 is likely to be the most important cytokine involved in the clinical efficacy of immunotherapy, and the suppression of allergen-induced IL-5 synthesis is most likely to be involved in the mechanism of immunotherapy. Our recent investigations, focusing on specific IgE and IgG4 responses, suggest that immunotherapy-induced changes in these specific antibodies play a clinical role and are involved in the mechanism of action of immunotherapy. It is probable that immunotherapy modulates and affects many different immunological and non-immunological phenomena to produce clinical efficacy and that clinical improvement is a consequence of different mechanisms over time.