Abstract
Inflammation plays a central role in the development of asthma, which is considered an allergic disease with a classic Th2 inflammatory profile. However, cytokine IL-17 has been examined to better understand the pathophysiology of this disease. Severe asthmatic patients experience frequent exacerbations, leading to infection, and subsequently show altered levels of inflammation that are unlikely to be due to the Th2 immune response alone. This study estimates the effects of anti-IL-17 therapy in the pulmonary parenchyma in a murine asthma model exacerbated by LPS. BALB/c mice were sensitized with intraperitoneal ovalbumin and repeatedly exposed to inhalation with ovalbumin, followed by treatment with or without anti-IL-17. Twenty-four hours prior to the end of the 29-day experimental protocol, the two groups received LPS (0.1 mg/ml intratracheal OVA-LPS and OVA-LPS IL-17). We subsequently evaluated bronchoalveolar lavage fluid, performed a lung tissue morphometric analysis, and measured IL-6 gene expression. OVA-LPS-treated animals treated with anti-IL-17 showed decreased pulmonary inflammation, edema, oxidative stress, and extracellular matrix remodeling compared to the non-treated OVA and OVA-LPS groups (p < 0.05). The anti-IL-17 treatment also decreased the numbers of dendritic cells, FOXP3, NF-κB, and Rho kinase 1- and 2-positive cells compared to the non-treated OVA and OVA-LPS groups (p < 0.05). In conclusion, these data suggest that inhibition of IL-17 is a promising therapeutic avenue, even in exacerbated asthmatic patients, and significantly contributes to the control of Th1/Th2/Th17 inflammation, chemokine expression, extracellular matrix remodeling, and oxidative stress in a murine experimental asthma model exacerbated by LPS.
Highlights
Bronchial asthma is an inflammatory, obstructive, heterogeneous, complex, and chronic lung disease characterized by an increase in mucus secretion and hyperreactivity of the airways
The OVA group treated with anti-IL-17 (41.93 ± 0.60) and the OVA-LPS group treated with anti-IL-17 (42.29 ± 0.51) had no significant differences compared to the OVA and OVA-LPS groups
The total cell count in the Bronchoalveolar Lavage Fluid (BALF) and the differential count for macrophages, lymphocytes, neutrophils, and eosinophils are shown in Figures 3A–E The evaluation of the total and the differential cell counts for macrophages, neutrophils, and eosinophils revealed an increase of type cells in the OVA and OVA-LPS groups compared to the SAL group (p < 0.05)
Summary
Bronchial asthma is an inflammatory, obstructive, heterogeneous, complex, and chronic lung disease characterized by an increase in mucus secretion and hyperreactivity of the airways. It has little toxicity when used directly to treat cells (in vitro). The use of this endotoxin provides information on the effects of the inflammatory response by bacterial infection [3]. Starkhammar et al [4] used an experimental model with a low dose of LPS (0.1 mg/ml) and found increased airway hyperresponsiveness and neutrophil-dominant inflammation, which is common in asthmatic patients with exacerbations caused by bacteria. The use of LPS in high doses reproduces a experimental model of acute lung injury [5]
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