PREVENTIVE EFFECT OF THYMIC ESTROMAL LYMPHOPOIETIN INHIBITION IN INFLAMMATION AND PULMONARY VASCULAR REMODELING IN EXPERIMENTAL MODEL OF CHRONIC ALLERGIC LUNG INFLAMMATION EXACERBATED BY LIPOPOLYSACCHARIDE

• Grant number: 24/04798-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2024
• Effective date (End): July 31, 2025
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Iolanda de Fátima Lopes Calvo Tibério
• Grantee: Paulo José Pouparina Canedo
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Introduction: In Brazil, asthma is a disease whose symptoms prevail in around 20% of adolescents, one of the highest international rates. Of those affected by this disease, 51.2% do not have their symptoms controlled and only 12.3% are completely controlled. Therefore, new ways of interfering in the course of this disease are important, given that it presents high morbidity and mortality and a high cost to health systems, reaching a value of US$ 170 million to the public health system due to hospitalizations. In order to try to achieve better control population results, this study proposes to evaluate the response to the acute effect of inhibiting TSLP, a protein that mediates hyperresponsiveness and modulates the inflammatory process of asthma, which presents itself as a possible new therapeutic target for controlling this disease. In this study, we must evaluate the vascular changes that, recently, have received great attention in understanding the pathophysiology of difficult-to-control asthma and that appear to be modulated by TSLP. This makes TSLP a potential therapeutic target for controlling vascular remodeling in patients with asthma. Objective: To evaluate the acute effect of TSLP inhibition on modulating inflammation and pulmonary vascular remodeling in murine models of OVA-induced asthma exacerbated by LPS. Materials and methods: In this study, BALB/c mice will be separated into six experimental groups: OVA, SAL, SAL-antiTSLP, OVA-antiTSLP, OVA-LPS, OVA-LPS-antiTSLP. They will undergo evaluation of the mechanics of the respiratory system, and evaluation of histopathology and immunohistochemistry using conventional morphometry of lung tissue, with emphasis on pulmonary vessels. Expected results: We hope to provide better clarification regarding the potential of TSLP to neutralize inflammation and vascular remodeling in asthma, so that this can contribute to the development of new therapies for asthma.