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

Abstract

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.

Animal models of asthma: utility and limitations

“…In rodent models, Th2 cytokine profile (interleukin 4 [IL-4], IL-5 and IL-13) has been well documented. 15 , 20 , 32 In a feline model, IL-4 has been demonstrated in airway allergic inflammation, 33 while in a sheep asthma model recently published, it has been demonstrated that both IL-4 and IL-13 increase in BAL after allergen challenge. 34 In equines, former studies were controversial in terms of inflammation pattern, ranging from Th1, Th2 and Th17 cytokines profile, 35 , 36 but recent studies have shown that inflammation seems to be mainly mediated by Th17 cytokines, like CXCL13 and IL-17.…”

“…Once IgE is produced, it will bind to the high-affinity receptor FcεR1 on the surface of mast cells and basophils. 32 , 33 …”

Anti-Inflammatory Effects of a Cordyceps sinensis Mycelium Culture Extract (Cs-4) on Rodent Models of Allergic Rhinitis and Asthma

“…A recent study has demonstrated that treating neonatal Sprague Dawley rats with capsaicin can result in an asthma-like phenotype, as evidenced by changes in the IgE levels; an increased number of eosinophils in the BAL fluid; and the increased mRNA expression of Th2 cytokines (such as IL-4, IL-5, and IL-13) in the lung tissue, as well as decreased airway resistance and compliance [ 46 ].…”

“…IgE levels in the plasma and in the supernatant produced from the BAL fluid were measured using a rat IgE ELISA kit (Cusabio, Houston, TX, USA) [ 46 ].…”

Anti-inflammatory and anxiolytic activities of Euphorbia hirta extract in neonatal asthmatic rats

“…Asthma is a well-known chronic disease of the lungs that affects the airways (Martinez 2007 ). Primary symptoms of asthma include bronchospasm, airflow obstruction, chest tightness, coughing, wheezing, and shortness of breath (Han et al 2017 ). Asthma cannot be cured permanently; only the symptoms can be ameliorated by medications (Han et al 2017 ).…”