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J Asthma Allergy. 2017 May 18;10:181-189. doi: 10.2147/JAA.S124902. eCollection 2017.

Asthma-like airway inflammation and responses in a rat model of atopic dermatitis induced by neonatal capsaicin treatment.

Han RT1,2, Kim S3, Choi K1,2, Jwa H1,2, Lee J1,2, Kim HY1,2, Kim HJ4, Kim HR5, Back SK6, Na HS1,2.

Author information

1
Neuroscience Research Institute.
2
Department of Physiology.
3
Department of Microbiology, College of Medicine, Korea University, Seoul.
4
Division of Biological Science and Technology, Science and Technology College, Yonsei University Wonju Campus, Wonju.
5
Department of Anatomy, College of Medicine, Seoul National University, Seoul.
6
Department of Pharmaceutics and Biotechnology, College of Medical Engineering, Konyang University, Chungnam, South Korea.

Abstract

Recent studies have shown that approximately 70% of patients with severe atopic dermatitis (AD) develop asthma. Development of AD in infancy and subsequent other atopic diseases such as asthma in childhood is referred to as atopic march. However, a causal link between the diseases of atopic march has remained largely unaddressed, possibly due to lack of a proper animal model. Recently, we developed an AD rat model showing chronically relapsing dermatitis and scratching behaviors induced by neonatal capsaicin treatment. Here, we investigated whether our model also showed asthmatic changes, with the aim of expanding our AD model into an atopic march model. First, we confirmed that capsaicin treatment (50 mg/kg within 24 h after birth) induced dermatitis and scratching behaviors until 6 weeks of age. After that, the mRNA expression of Th1 and Th2 cytokines, such as IFN-γ and TNF-α, and IL-4, IL-5, and IL-13, respectively, was quantified with quantitative real-time polymerase chain reaction in the skin and the lungs. The number of total cells and eosinophils was counted in bronchoalveolar lavage (BAL) fluid. The levels of IgE in the serum and BAL fluid were determined with enzyme-linked immunosorbent assay. Paraffin-embedded sections (4 μm) were stained with hematoxylin/eosin to analyze the morphology of the lung and the airway. Airway responsiveness was measured in terms of airway resistance and compliance using the flexiVent system. In the capsaicin-treated rats, persistent dermatitis developed, and scratching behaviors increased over several weeks. The levels of IgE in the serum and BAL fluid as well as the mRNA expression of Th2 cytokines, including IL-4, IL-5, and IL-13, in both the skin and the lungs were elevated, and the number of eosinophils in the BAL fluid was also increased in the capsaicin-treated rats compared to control rats. Morphological analysis of the airway revealed smooth muscle hypertrophy and extensive mucus plug in the capsaicin-treated rats. Functional studies demonstrated an increment of the airway resistance and a decrement of lung compliance in the capsaicin-treated rats compared to control rats. Taken together, our findings suggested that neonatal capsaicin treatment induced asthma-like airway inflammation and responses in juvenile rats.

KEYWORDS:

BAL fluid; airway hypertrophy and remodelling; atopic march; cytokines; eosinophils; flexiVent; pruritus; scratching

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

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