"Effects of obesity in the exacerbation of chronic obstructive pulmonary disease (COPD) mediated by the Th17 immune response

• Grant number: 23/00549-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2023
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Fernanda Degobbi Tenorio Quirino dos Santos Lopes
• Grantee: Letícia de Paula Costa Mattos
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The importance of the adaptive immune response, characterized by an increase in Th17 lymphocytes, as well as interleukin-17 (IL-17) in the development and progression of chronic obstructive pulmonary disease (COPD), has already been described in the literature. The role of obesity in the exacerbation of different pre-existing diseases mediated by the TH17 response has also been described. Thus, in this study we intend to evaluate the immune response mediated by Th17 lymphocytes in an experimental model in which we will associate the administration of a high-fat diet to induce obesity in animals exposed to cigarette smoke to induce COPD. We also evaluated the effects of treatment with a specific inhibitor for IL-17 on lung functional and structural alterations resulting from the association of diet with the COPD induction model. Methods: Male C57BL/6 mice (6-8 weeks) from the Central Animal Facility of the USP Medical School (FMUSP) will be used and will be divided into six groups: A= control group; B= anti-IL-17 control group; C= smoking group; D = anti-IL-17 smoking group; E= smoking and obesity group; F = anti-IL-17 smoking/obesity group. The animals will be exposed to cigarette smoke twice a day, 5 days a week, for 6 months. Control animals remained in the vivarium. The experimental protocol will be conducted with a high-fat diet and a control diet. The neutralizing antibody for IL-17 will be administered twice a week and 1 hour before exposure to cigarette smoke at the end of the fifth month of the experimental protocol. For the evaluation of parameters that characterize obesity, body mass and food intake will be measured twice a week. The glucose tolerance test (GTT) or insulin tolerance test (ITT) was performed in the last week of the protocol, as previously described. At the end of the exposure protocol, the animals in each group will be anesthetized with Thiopental, tracheostomized and connected to a respirator, for evaluation of respiratory mechanics parameters. Still under the effect of anesthesia, the animals will be euthanized for later collection of the lungs and preparation of histological slides for the evaluation of the mean linear intercept.