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

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.

The efficacy of sublingual immunotherapy with Dermatophagoides farinae vaccine in a murine atopic dermatitis model

“…Desensitization was performed simultaneously with sensitization step from 0 to 8 week in accordance with the following procedure (Table 1), and this procedure was refer to Der f drops' clinical application [14]. The Der f drops (Chanllergen) was provided by Zhejiang Wolwo Bio-Pharmaceutical Co., Ltd. [15].…”

T helper subsets in allergic eye disease

“…In a mouse model of ocular allergy using Dermatophagoidesfarinae , sublingual immunotherapy (SLIT) reduced clinical symptoms and the associated Th2 responses (110). Interestingly, SLIT in patients with allergic asthma to the same allergen had reduced symptoms that correlated with reduced Th17 cells and increased Tregs (111).…”

Comparative analysis of the oral mucosae from rodents and non-rodents: Application to the nonclinical evaluation of sublingual immunotherapy products

“…In addition, the presence of a glycogen-rich content in the cytoplasm of epithelial cell detected only in minipigs and monkeys also supports the inference that such cells are similar to those of humans. In line with these observations, several studies conducted in allergy murine models showed that higher doses (fifty to a hundred times more) of allergen are required for a successful treatment in allergic mice when compared to doses administered to humans in the course of AIT [ 31 – 37 ]. Consequently, such models only approximate the human situation regarding allergen dosage and administration schemes.…”