|1758-1||ANTI-INFLAMMATORY ROLE OF ATORVASTATIN IN A MODEL OF MICE PNEUMONIA.
|Autores:||Talles Prosperi de Paula (UFMG - Universidade Federal de Minas Gerais) ; Raquel Duque do Nascimento Arifa (UFMG - Universidade Federal de Minas Gerais) ; Angélica Tavares Vieira (UFMG - Universidade Federal de Minas Gerais) ; Thiago Vinícius Ávila (UFMG - Universidade Federal de Minas Gerais) ; Mauro Martins Teixeira (UFMG - Universidade Federal de Minas Gerais) ; Danielle da Glória de Souza (UFMG - Universidade Federal de Minas Gerais) |
Introduction: Klebsiella pneumoniae is a gram negative bacterium involved in many nosocomial diseases like pneumonia. Statins are inhibitors of coenzyme HMG-CoA that act in the control of plasmatic cholesterol levels and cardiovascular diseases. Recent clinical studies describe pleiotropic effects of some statins in survival increase of patients with respiratory diseases. Here, we show atorvastatin as an adjuvant to control inflammatory responses after experimental pneumonia.
Methods: This project was approved by CETEA/UFMG. Female C57/BL6 (8-12 weeks) were pre-treated with 10mg/kg of atorvastatin or vehicle 24h before infection. We infected mice with Klebsiella pneumoniae ATCC-27736 after anesthesia with xylazine/ketamine. 30 µL of a suspension containing 3 X 106 CFU/mL of K. pneumoniae or saline was administered intranasally. Mice were submitted to survival experiments or sacrificed 24h after infection. Blood and lungs were harvested to analyse MPO levels, cytokines and chemokine levels, histopathological analysis and bacterial loads. BAL was performed to reach polimorfonuclear infiltration and the cytokine/chemokynes.
Results and discussion: Lethality started on the 3th day after infection and percentage was 75% after 14 days. Use of atorvastatin delayed lethality to the 7th day and enhanced survival in 50% in comparision to control groups. 24 hours after infection mice treated with vehicle presented increased number of neutrophils in the broncoaveolar fluid and myeloperoxidase levels in the lungs. We also detected increased levels of TNF-α, IL-6 and chemokine CXC-1 in BAL and lungs. Pre-treatment with atorvastatin decreased neutrophils and levels of citokynes and chemokynes in broncoalveolar fluid and lungs. We observed more intense cell infiltration in the histopathology analysis of mice treated with vehicle in comparision with treated groups. Nevertheless, we did not observe differences in the bacterial loads recovered in any of the groups treated with vehicle or atorvastatin.
Conclusion: Our results demonstrated that atorvastatin modulates inflammatory responses in the early stages of pulmonary K. pneumoniae infection in mice.
Finantial support: CAPES, CNPq and FAPEMIG.
Palavras-chave: Klebsiella pneumoniae, atorvastatin, inflammation