Clinical & Experimental Allergy

Mucosal tolerance as therapy of type I allergy: intranasal application of recombinant Bet v 1, the major birch pollen allergen, leads to the suppression of allergic immune responses and airway inflammation in sensitized mice

Authors


Ursula Wiedermann, Departments of Clinical Pharmacology and Pathophysiology, University of Vienna, AKH, Waehringer Guertel 18–20, A-1090 Vienna, Austria. E-mail: ursula.wiedermann@akh-wien.ac.at

Abstract

Background Several studies have demonstrated that mucosal administration of soluble antigens can prevent the onset or reduce the severity of certain autoimmune diseases or allergies. Few studies exist showing the efficacy of mucosal tolerance for therapy of such diseases.

Objective The aim of the present study was to modulate an allergic immune response by intranasal antigen administration in an already sensitized organism.

Methods A murine model of allergic asthma to birch pollen (BP) and its major allergen Bet v 1 was utilized. Sensitized mice were intranasally treated with recombinant (r)Bet v 1 in different concentrations and at different intervals. On the day the mice were killed, blood and bronchoalveolar lavage fluids were taken and immediate type I skin tests were performed. T cell proliferation and cytokine production (interleukin (IL)-5, interferon (IFN)-γ) were measured in spleen and lung cell cultures.

Results Mucosal treatment with rBet v 1 (3 × 50 µg in 4 day intervals) led to a reduction of type I skin reactions, suppressed immunoglobulin (Ig)G1/IgE antibody levels and markedly decreased IL-5 and IFN-γ production in vitro in spleen and lung cell cultures. Moreover, lung inflammation (i.e. eosinophilia and IL-5 levels in bronchoalveolar lavage fluids) was significantly suppressed by the treatment.

Conclusion Our results demonstrate that intranasal treatment with rBet v 1 reduced systemic allergic immune responses as well as airway inflammation in BP-sensitized mice. We therefore suggest that mucosal tolerance induction with recombinant allergens could be a promising concept for the therapy of allergic diseases.

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