[Show abstract][Hide abstract] ABSTRACT: Allergen-specific sublingual immunotherapy is a potential treatment for allergic diseases. Its effective dose and underlying mechanism are still to be explored. Here, we investigated the efficacy and mechanism of sublingually administered Dermatophagoides farinae (Der f) vaccine in a murine asthma model.
BALB/c mice were sensitized intraperitoneally with Der f extract absorbed to alum, followed by sublingual treatment with Der f vaccine for 6 weeks. The mice were subsequently challenged intranasally with Der f extract for 1 week. We analyzed their clinical symptoms, antibody levels, cytokine levels, T-cell proliferation and the regulatory T-cell numbers.
Mice treated with high-dose Der f sublingual vaccine prior to challenge displayed alleviated symptoms such as airway hyperreactivity, lung inflammation and mucus production, as well as less eosinophilic cells in bronchoalveolar lavage fluid. Interestingly, reduced responses of Der-f-specific IgE and increased responses of Der-f-specific IgA and IgG1 were aroused in the high-dose Der f sublingual vaccine group. We also observed that interleukin-4 was reduced and interferon-gamma and interleukin-10 were increased among splenocytes and in bronchoalveolar lavage fluid, which inhibited Der-f-specific T-cell proliferation of the spleen and increased CD4+CD25+Foxp3+regulatory T cells in the spleen. However, mice treated with low-dose Der f sublingual vaccine developed allergic asthma.
Our results illustrate that high-dose Der f sublingual vaccine may play a role in immunologic protection in murine allergic asthma, possibly by inducing regulatory T cells and Th1 reaction.
No preview · Article · Nov 2009 · International Archives of Allergy and Immunology
[Show abstract][Hide abstract] ABSTRACT: To study the therapeutic effect on murine allergic asthma with recombinant Bla g 2 (rBla g 2) allergen and its possible mechanism.
Eighteen BALB/C mice were randomly divided into three groups: normal control group (group A), asthma model group (group B), and recombinant protein rBlag2 treatment group (group C). Mice in groups B and C were subcutaneously immunized weekly with rBla g 2 (50 mg) formulated in Al (OH)3 adjuvant for three weeks. Group A received only adjuvant emulsified with normal saline. Two weeks after the last inoculation, mice in group C were administered each with rBla g 2 (100 mg) /dose, and groups A and B were given PBS. All the mice received eight doses at 2-day intervals. One week after the last immunotherapy, mice in groups B and C were intranasally challenged with 50 mg rBla g 2 daily for seven days, while mice in group A received PBS. Twenty-four hours after the challenge, the following items were examined: airway hyperresponsiveness of mice, total cellular score and cell classification in bronchoalveolar lavage fluid (BALF), level of rBla g 2-specific IgE and IgG2a in serum, lung inflammation by HE stain, and Bcl-2 expression of eosinophils of lung by immunohistochemistry.
Compared with group B, group C showed a decreased Penh value of airway hyperresponsiveness (P < 0.05), reduced serum rBla g 2-specific IgE but increased IgG2a (P < 0.01), and reduced Bcl-2 expression of eosinophils. Total cells [(24.60 +/- 15.08) x 10(5)/ml] and eosinophils [(22.20 +/- 3.76) x 10(5)/ml] in BALF of group B significantly increased than those of group C [(14.30 +/- 4.95) x 10(5)/ml and (5.20 +/- 1.56) x 10(5)/ml, respectively] (P < 0.01). The interstitial space surrounding the airway lumen was characterized by a densely mixed cellular infiltrate, tissue edema and epithelium tissue damage in group B, while lung inflammation of group C reduced considerably. Each test value of group C was substantially similar to that of group A.
The experiment shows proper immunotherapeutic efficacy of rBla g 2 in murine allergic asthma, which may possibly related to the apoptosis of eosinophils.
No preview · Article · Apr 2009 · Zhongguo ji sheng chong xue yu ji sheng chong bing za zhi = Chinese journal of parasitology & parasitic diseases