The effects of anti-IL-17 on bronchial vascular remodeling in an asthma and COPD overlap model (ACO)

• Grant number: 23/06746-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2023
• Effective date (End): June 30, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Iolanda de Fátima Lopes Calvo Tibério
• Grantee: Bruno André Rampinelli
• 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-COPD overlap (ACO) is an airway disease characterized by fixed obstruction to airflow with features common to both asthma and COPD, but a more specific definition could not yet be established, given the lack of scientific evidence. on the subject. One of the most relevant implications in the diagnosis and understanding of the pathophysiology of ACOS is the therapy and modulation mechanisms to be adopted for these patients and based on all these similarities and differences in the definition and pathophysiology of ACOS, it is understandable that further investigations are needed. scientific studies related to this disease. Thus, the main objective of this project is to study the effects of anti-IL-17 in the modulation of pulmonary vascular remodeling in an experimental model of ACO. For this, an experimental model of ACO will be carried out with the following experimental groups: SAL group (inhalations with saline solution); OVA group (inhalations with ovalbumin solution); OVA-anti-IL-17 group (inhalations with ovalbumin solution and treatment with anti-IL-17 monoclonal antibody); ALS group (intratracheal instillations of elastase); anti-IL-17 ALS group (intratracheal instillations of elastase and treatment with anti-IL-17 monoclonal antibody); ACO group (inhalations with OVA solution and intratracheal instillations of elastase) and ACO-anti-IL-17 group (inhalations with OVA solution, intratracheal instillations of elastase and treatment with anti-IL-17 monoclonal antibody). After sensitization of mice, euthanasia and lung extraction will be performed to perform ELISA and immunohistochemistry techniques for the following markers: evaluation of anti- and pro-inflammatory cytokines (IL-10, IL-4, IL-1b, IL-17); extracellular matrix elements: type I, III, V and TIMP-1 collagen fibers; peribronchovascular edema; angiogenesis and vascular endothelial growth factor (VEGF).