PREVENTIVE EFFECT OF THYMIC STROMAL LYMPHOPOIETIN INHIBITION IN AN EXPERIMENTAL MODEL OF CHRONIC ALLERGIC PULMONARY INFLAMMATION EXACERBATED BY LIPOPOLYSACCHARIDE

• Grant number: 23/10674-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): November 01, 2023
• Effective date (End): October 31, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Iolanda de Fátima Lopes Calvo Tibério
• Grantee: Vitor de Paula Casagrande
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 18/02537-5 - Characterization of asthma-COPD overlap syndrome (ACOS): experimental and clinical studies, AP.TEM

Abstract

Asthma is a chronic inflammatory lung disease characterized by recurrent episodes of airway obstruction, hyperresponsiveness, and inflammation of the airways. According to epidemiological studies in Brazil, 23% of asthmatic patients aged between 18 and 45 years experienced signs and symptoms of asthma syndrome in the last year, such as dyspnea, wheezing, cough, and retrosternal chest tightness. Additionally, a research by Cançado et al. observed that over half of the diagnosed asthma patients were clinically uncontrolled. As a result, many studies on asthma's pathophysiology are being conducted to better understand the inflammatory process of this disease, enabling the development of new methods for clinical control of the asthmatic syndrome. In this context, various clinical and experimental evidence suggests the importance of thymic stromal lymphopoietin (TSLP) in the hyperresponsiveness and modulation of the inflammatory process present in asthma, as well as its role in the development and progression of asthma syndrome due to its involvement in the disease's inflammatory processes. However, the effects of acute TSLP inhibition are still unknown, necessitating a study on TSLP as a possible signaling pathway and pathogenesis of asthma and its potential as a therapeutic target. This study aims to evaluate the acute effect of TSLP inhibition on the modulation of inflammation, oxidative stress, and tissue remodeling of the airways and lung parenchyma in murine models of OVA-induced asthma exacerbated by lipopolysaccharides (LPS). For this purpose, after approval from the Ethics Committee for Research at the Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo, the study will use 84 male BALB/c mice as the experimental model. The animals will be treated following the Guide for the Care and Use of Laboratory Animals, published by the National Institute of Health (NIH publication 85-23, revised in 1985). The animals will be divided into six groups, receiving different injections, inhalations, and/or instillations. After this phase, all animals will undergo a process of inducing chronic allergic lung inflammation, with two groups also receiving LPS administration. Subsequently, the mice will be treated with 20 µg of anti-TSLP. There will be an evaluation of respiratory mechanics, bronchoalveolar lavage fluid, lung histopathology, and immunohistochemistry of these animals. Finally, morphometric analysis will be conducted using the point counting technique and statistical analysis using the SigmaStat program (SPSS Inc, Chicago, IL). The Student-Newman-Keuls test will be used for results with parametric distribution, and the Kruskal-Wall test for results with non-parametric distribution, with P<0.05 being considered as statistically significant.