Sublingual immunotherapy reduces allergic symptoms in a mouse model of rhinitis.
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.


CONCLUSIONS
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.
Brimnes
J
J
Department of Experimental Immunology, ALK-Abelló A/S, Hoersholm, Denmark. jeb@dk.alk-abello.com
Kildsgaard
J
J
Jacobi
H
H
Lund
K
K
D000286:Administration, Sublingual; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D000818:Animals; D052179:Antigens, Plant; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007073:Immunoglobulin E / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D010940:Plant Proteins; D011058:Pollen / Q000276:immunology; D012220:Rhinitis / Q000276:immunology / Q000628:therapy*; D018418:Th2 Cells / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome
D000485:Allergens; D052179:Antigens, Plant; D016207:Cytokines; D010940:Plant Proteins; C485292:ph1p 1 allergen, timothy grass; D007073:Immunoglobulin E