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Preventive and therapeutic effect of anti-IL-17 in experimental model of pulmonary lesion induced by elastase in C57BI6 mice

Grant number: 17/15495-6
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2017
Effective date (End): August 31, 2019
Field of knowledge:Biological Sciences - Physiology
Principal Investigator:Iolanda de Fátima Lopes Calvo Tibério
Grantee:Aurelio Canabrava Garrido
Home Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Chronic Obstructive Pulmonary Disease (COPD) is a respiratory disease that is preventable and treatable. The particles generated by tobacco smoke are the most frequent sources of establishment of the disease, by the inflammatory response produced by the lung tissue against these particles. Currently, the most important management strategies are cessation of smoking, vaccination, rehabilitation and drug therapy (mainly by inhalation). Some patients, however, may require long-term oxygen therapy or even lung transplantation. It is the fourth leading cause of death in the United States, and the largest cause of chronic morbidity on the elderly, posing a major public health challenge. It has been ranked as the sixth leading cause of death in the world in 1990 and is projected to be the third leading cause in 2020. Evidently, because of the high economic burden due to health care costs and loss of productivity, this disease has been being well studied, with the search of medicines and biomarkers for the early diagnosis being of utter importance. Emphysema, a component of COPD, is characterized as a lung disorder in which there is a permanent enlargement in terminal air spaces due to the destruction of the alveolar walls. The destruction of lung tissue is a result of the imbalance between the proteinases systems, produced in the inflammatory process, and antiproteinases. This mechanism of lung injury can be induced in experimental model by administration of intratracheal elastase in mice.IL-17A, the major cytokine product of Th17 cells, plays an important role in regulating the expression of inflammatory mediators and recruitment of inflammatory cells in various diseases, including emphysema. This study aims to evaluate the effect of the preventive and therapeutic approach of the administration of anti-IL-17 monoclonal antibody in experimental model of lung injury induced by elastase in lungs of mice. The results will be analyzed from pulmonary mechanics, exhaled nitric oxide and microscopic observation of alveolar diameter, macrophagic inflammatory response and, by immunohistochemistry, inflammatory markers in different groups of mice. The groups will be control (who will receive only intratracheal saline injection), elastase control (who will only receive intratracheal elastase), preventive (receive anti-IL-17 along with elastase instillation) and the treatment group (antibody as treatment for emphysema after a certain period).It is expected that this study will yield significant results on the preventive and therapeutic effect of the use of the anti-IL-17 monoclonal antibody on the pathophysiology of pulmonary emphysema and help in the creation of new strategies for approaching this currently relevant disease. (AU)