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Sublingual immunotherapy reduces allergic symptoms in a mouse model of rhinitis

Authors


Correspondence:
Jens Brimnes, Department of Experimental Immunology, ALK-Abelló A/S, Boege Alle 6-8, DK-2970 Hoersholm, Denmark.
E-mail: jeb@dk.alk-abello.com

Summary

Background Sublingual immunotherapy (SLIT) is a clinically effective treatment in both pollen and house dust mite-induced rhinitis and asthma. However, the mechanisms by which this is accomplished are not clear.

Objective The objective of the current study was to establish a mouse model of rhinitis in order to study the effect and mechanisms of SLIT.

Methods Mice were sensitized by intraperitoneal injections of alum-adsorbed Phleum pratense extract. Sensitized mice were SLIT-treated and subsequently challenged intranasally and analysed for clinical symptoms, antibody levels, eosinophilia and T cell response.

Results Intranasal challenge of sensitized mice led to the development of rhinitis characterized by significantly increased sneezing and influx of eosinophils into the nose. Levels of specific IgE were fivefold increased in nasopharyngeal lavage (NAL) fluid and more than doubled in serum. Furthermore, a T-helper type 2 (Th2) like T cell response was observed in local draining lymph nodes. SLIT treatment of sensitized mice reduced sneezing, eosinophilia and IgE levels in the NAL by more than 50%. Moreover, serum levels of IgE and IgG1 as well as T cell response in the draining lymph nodes were also significantly reduced. Treatment for a shorter time or with a lower dose only led to minor reductions of the clinical and immunological parameters, indicating that the effect of SLIT is time and dose dependent.

Conclusion In the present study, we have established a mouse model displaying the hallmarks of allergic rhinitis using a clinically relevant allergen. Using this model, we have demonstrated that SLIT treatment is able to reduce allergic symptoms in a time- and dose-dependent manner.

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