Oral administration of allergen extracts from Dermatophagoides farinae desensitizes specific allergen-induced inflammation and airway hyperresponsiveness in rats.
Clinically sublingual immunotherapy (SLIT) by using allergen extracts effectively alleviates the symptoms of allergic rhinitis and asthma. Supposed that oral administration of high-dose of allergen extracts imitates SLIT and may prevent IgE-related responses in allergic diseases, we investigated the effects of oral administration of allergen extracts from Dermatophagoides farinae (Derf) on allergen-induced inflammation and airway hyperresponsiveness (AHR) in a model of asthmatic rat. After administration to the specific Derf-sensitized rats with Derfdrop solution containing Derf1 and Derf2 extracts derived from Derf, the effects of Derfdrop on AHR, inflammatory cell accumulation, cytokine production in the bronchoalveolar lavage fluid and lung tissue, as well as serum IgE and IgG levels were investigated. Results indicated that Derfdrop not only dose-dependently prevented the AHR in response to methacholine, but also significantly reduced the serum total and allergen-specific IgE levels, all the maximal effects were achieved at dose of 5 mg/kg/d, and were as comparable as those of dexamethasone at dose of 1.0 mg/kg/d. Furthermore, oral administration of Derfdrop not only dose-dependently elevated allergen-specific serum IgG levels and reduced total and allergen-specific IgE levels, but also normalized the imbalance between the Th1 cytokine, IFN-gamma and Th2 cytokine, IL-4. Finally, oral administration of Derfdrop significantly reduced Goblet cell hyperplasia and eosinophilia in the Derf-sensitized allergic rat model. These data suggest that Derfdrop effectively improves specific allergen-induced inflammation and AHR in Derf-sensitized and -challenged rats and provide with the rationale for clinical SLIT by using Derfdrop in a specific allergen-induced asthma.
Xie
Qiang-min
QM
Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration, Medical Science College of Zhejiang University, 388 Yuhangtang Rd. Hangzhou City, Zhejiang Province 310058, PR China. xieqm@zju.edu.cn
Wu
Ximei
X
Wu
Hui-min
HM
Deng
Yang-mei
YM
Zhang
Shui-juan
SJ
Zhu
Jian-ping
JP
Dong
Xin-wei
XW
D000284:Administration, Oral; D000818:Animals; D001249:Asthma / Q000628:therapy*; D016535:Bronchial Hyperreactivity / Q000628:therapy*; D040001:Dermatophagoides farinae / Q000276:immunology*; D003888:Desensitization, Immunologic; D004802:Eosinophilia / Q000517:prevention & control; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley
D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma