• Jochen Grommes, Santosh Vijayan, Maik Drechsler, Helene Hartwig, Matthias Mörgelin, Rolf Dembinski, Michael Jacobs, Thomas Andreas Koeppel, Marcel Binnebösel, Christian Weber, and Oliver Soehnlein.
• Institute for Molecular Cardiovascular Research (IMCAR), RWTH Aachen, Aachen, Germany. jgrommes@ukaachen.de
• Plos One. 2012 Jan 1;7(6):e38917.

IntroductionTreatment of acute lung injury (ALI) remains an unsolved problem in intensive care medicine. As simvastatin exerts protective effects in inflammatory diseases we explored its effects on development of ALI and due to the importance of neutrophils in ALI also on neutrophil effector functions.MethodsC57Bl/6 mice were exposed to aerosolized LPS (500 µg/ml) for 30 min. The count of alveolar, interstitial, and intravasal neutrophils were assessed 4 h later by flow cytometry. Lung permeability changes were assessed by FITC-dextran clearance and albumin content in the BAL fluid. In vitro, we analyzed the effect of simvastatin on neutrophil adhesion, degranulation, apoptosis, and formation of reactive oxygen species. To monitor effects of simvastatin on bacterial clearance we performed phagocytosis and bacterial killing studies in vitro as well as sepsis experiments in mice.ResultsSimvastatin treatment before and after onset of ALI reduces neutrophil influx into the lung as well as lung permeability indicating the protective role of simvastatin in ALI. Moreover, simvastatin reduces the formation of ROS species and adhesion of neutrophils without affecting apoptosis, bacterial phagocytosis and bacterial clearance.ConclusionSimvastatin reduces recruitment and activation of neutrophils hereby protecting from LPS-induced ALI. Our results imply a potential role for statins in the management of ALI.

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