Abstract
The efficacy of specific immunotherapy in the treatment of allergic rhinitis is now clearly established. The fundamental principle of this form of therapy is still not fully understood, although considerable advances have been made in clarifying various aspects of the mechanisms of action. An important effect of the therapy is the inhibition of migration of inflammatory cells into the mucosa. The results of in vitro investigations and characterization of the cytokine profiles in biopsy specimens from skin and nasal mucosa at the time of an allergeninduced late-phase reaction support the view that reorientation of a Th2 lymphocyte immune response in the direction of a Thl reaction is a fundamental aspect of the mechanisms of the immunotherapy. In order to further clarify the reasons for the cellular infiltration and to obtain evidence for the postulated Th2/Th1 switch in the nasal mucosa, we have measured various cytokines in the nasal secretions from 34 grass-allergic patients participating in a randomized double-blind, placebo-controlled study of specific immunotherapy. One group of 17 patients was treated with a grass pollen allergoid preparation (Allergovit®), whilst the other group received a histamine-containing placebo. Cytokine determinations were performed using enzyme-linked immunosorbent assays with nasal lavage samples obtained before the beginning of therapy and at three time points during the pollen season. Interleukins (IL) 4 and 5 are typical Th2 cytokines effecting the stimulation of IgE synthesis and the activation and differentiation of eosinophil granulocytes, respectively, but they were not detectable in significant amounts in the nasal secretions. Therefore, the investigation did not provide evidence for a T helper cell switch. IL-1Β, IL-6, and IL-8 were consistently detectable. Specific immunotherapy had no effect on the nonspecific proinflammatory cytokine IL-6. There were significant reductions in the concentrations of the chemokine IL-8 (p < 0.05) and the important proinflammatory cytokine IL-1Β (p < 0.005) in nasal secretions from the treatment group during the pollen season, but not in the placebo group. These two cytokines play an important role in transendothelial cell migration, and their reduced concentrations as a result of the specific immunotherapy may contribute at least in part to the inhibition of inflammatory cell migration into the nasal mucosa. These observations are in keeping with the anti-inflammatory effect of the specific immunotherapy.
Published Version
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