Efeito do tratamento com atorvastatina na pneumonia experimental induzida por Klebsiella pneumoniae em camundongos

Abstract

The clinical pathogen Klebsiella pneumonia has still been involved in many nosocomial infections and resistance to the present carbapenic antibiotic treatments. Statins are inhibitors of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) well known for controlling plasmatic cholesterol levels and cardiovascular diseases. Some clinical evidences describe pleiotropic effects of some statins including therapeutic effects on the control of lung inflammation. Here, previous treatment with atorvastatin has shown to decrease cell influx of neutrophils and macrophages to the lungs and also pro-inflammatory cytokines levels in the initial phase of infection with K. pneumoniae in C57/BL6 mice. However, atorvastatin did not modify the number of bacteria in the lungs or in the blood, but decreased locally inflammatory responses. Treatment also increased phagocytosis of opsonized bacterium in the neutrophils present in bronchoalveoar space in vivo and macrophages in vitro. We also intriguingly demonstrated that atorvastatin did not alter ROS production by that phagocytic macrophages. Furthermore, mice post-treated with the combination of imipenem and atorvastatin had an important reduction in mortality compared to mice treated with vehicles, atorvastatin or imipenem alone. The present work hypothesized that pre- and conventional treatment with atorvastatin could be an adjuvant on the treatment of CAPS, capable of increasing survival and controlling initial inflammatory responses. Here, we suggest a screening of patients previously or regularly treated with this statin, in case of Gram negative pneumonia and when submitted to imipenem treatment.