Sublingual Immunotherapy for Experimental Allergic Conjunctivitis in a Murine Model Induced by Dermatophagoides farinae Allergen

Int Arch Allergy Immunol 2013; 161:205–212

Li-lin Liu, Dan-dan Guo, Qiao-xia Liang, Shan Ding, Jing-ya Chen, Bing Wu, Qin Li

Division of Research and Development, Wolwo Bio-Pharmaceutical Inc., Shanghai, PR China

 

Abstract

Background: Sublingual immunotherapy (SLIT) is a clinically effective treatment in allergic conjunctivitis (AC); however, the mechanism of the underlying pharmacodynamics remains unclear. Here, we investigate the efficacy and the mechanism of a sublingually administered Dermatophagoides farinae (Der f) vaccine in a murine AC model.

Methods: A murine model of AC caused by Der f extract was developed in BALB/c mice by repeated application of allergen. Sensitized mice were SLIT treated by Der f drops and subsequently analyzed for AC symptoms, histopathological and immunological parameters.

Results: In this study, Der f extract successfully induced the symptoms of AC in BALB/c mice. In these sensitized mice, clinical symptoms (scratching behavior, lacrimation, conjunctival hyperemia and edema), immunological and histopathological findings (inflammatory cell infiltration) were very similar to those in human AC. SLIT treatment of sensitized mice markedly reduced the clinical and histopathological symptoms and decreased the expression levels of total immunoglobulin E (IgE), Der f-specific IgE and T helper cell 2 (Th2) cytokine interleukin-4, with a significant increase in Der f-specific IgG4 and Th1 cytokine interferon-γ.

Conclusions: SLIT with Der f drops is a potentially effective means of immunotherapy for Der f-induced AC by modulating the Th2-biased allergic immune response.

 

Supplement

Perennial allergic conjunctivitis (AC) exhibits hypersensitivity to the common perennial house hold allergens, such as dust mites. AC was demonstrated to be a type Ⅰ hypersensitivity reaction, which was mediated by the classic IgE/mast cell. The current recommended treatments for AC were allergen avoidance and pharmacotherapy. But these treatments were not causal treatment for AC, and only have short–lasting efficacy. As sublingual immunotherapy (SLIT) has proved to be a causal treatment for type Ⅰ allergic disease, and SLIT’s efficacy on AC had been justified by several clinical studies, but rare studies had been performed to research the underlying mechanisms of SLIT, especially in mite-induced AC.

We developed an AC mouse model, that allergic to Dermatophagoides farinae (Der f), with similar symptoms and pathology to human AC (e.g. elevated scratching scores (itching); hyperemia/edema score; increased infiltrating eosinophils; a rise in IL-4 mRNA and Der f specific IgE levels), then firstly investigated the efficacy and mechanism of SLIT in this mouse model.

We found that SLIT had remarkable clinical efficacy in our AC mouse model (Figure 1). After SLIT, Der f specific IgE and IL-4 (Th2 cytokine) mRNA level were decreased; on the contrary, Der f specific IgG and IFN-γ (Th1 cytokine) mRNA level were increased significantly. The shift in Th1/Th2 balance might be the most important success in immunotherapy of AC induced by Der f allergen. In human therapeutic mechanism researches, SLIT could regulate the Th2 and Th1 responses, and induce the change in the level of IgE and IgG. Our results indicated that SLIT in AC may involve a mechanism similar to that in allergic respiratory diseases.

QIN LI

Figure 1. Clinical symptoms and scores in mice under different treatments. A Eye features. B Quantitative analysis of scratching behaviour. C Evaluation of conjunctivitis. Data represent the mean±SD. ##p<0.01, compared with mice in the control group; *p<0.05 and **p<0.01, compared with mice in the model group. Data are representative of three independent experiments.

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