IMMUNOTHERAPY SUPPRESSES BOTH TH1 AND TH2 RESPONSES BY ALLERGEN STIMULATION, BUT SUPPRESSION OF THE TH2 RESPONSE IS A MORE IMPORTANT MECHANISM RELATED TO THE CLINICAL EFFICACY OF IMMUNOTHERAPY FOR PERENNIAL ALLERGIC RHINITIS

Increased attention has recently been directed at the possibility that the clinical efficacy of immunotherapy might be elaborated by alterat ion of T-cell reactivity. However, there is no general agreement among different investigators regarding the effect of immunotherapy on Th-c ell reactivity. Peripheral blood mononuclear cells (PBMCs) from 15 non atopic subjects and 76 patients with perennial allergic rhinitis (18 u ntreated patients and 58 patients on immunotherapy) were cultured in t he absence and in the presence of a major Dermatophagoides farinae all ergen, Der f 1, and the levels of IgE, interleukin-5 (IL-5), interfero n-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) in the culture supernatants were determined. The difference between the abse nce and presence of Der f 1 was calculated to consider the Der f 1-dep endent synthesis of IgE, IL-5, IFN-gamma and TNF-alpha. The levels of Der f 1-dependent synthesis of IgE, IL-5 and TNF-alpha were significan tly higher in the untreated group than in the nonatopic group, whereas Der f 1-dependent synthesis of IFN-gamma was significantly lower in t he untreated group than in the nonatopic group. Immunotherapy decrease d the enhanced Der f 1-dependent synthesis of IgE, IL-5 and TNF-alpha, and further decreased the suppressed Der f 1-dependent synthesis of I FN-gamma as the therapy proceeded. The levels of Der f 1-dependent syn thesis of IgE and IL-5 did not differ between nonatopic individuals an d patients whose duration of immunotherapy was 10 or more years. The l evels of Der f 1-dependent synthesis of IgE and IL-5, but not of IFN-g amma and TNF-alpha, were correlated significantly with the levels of s ymptom scores. In addition, the levels of Der f 1-dependent synthesis of IgE and IL-5, but not of IFN-gamma and TNF-alpha, differed signific antly between good and poor responders. In conclusion, immunotherapy f or perennial allergic rhinitis may possibly work via induction of tole rance or anergy of both Th1- and Th2 cells. However, our study is like ly to support a view that the mechanisms responsible for the clinicall y beneficial effects of immunotherapy principally involve the toleranc e of Th2-rather than Th1 cells. In addition, suppression of IgE synthe sis is also likely to be linked to the clinical efficacy of immunother apy for perennial allergic rhinitis.