Abstract
BackgroundHeparin-binding protein is released by neutrophils during inflammation and disrupts the integrity of the alveolar and capillary endothelial barrier implicated in the development of acute lung injury and systemic organ failure. We sought to investigate whether oral administration of simvastatin to patients with acute lung injury reduces plasma heparin-binding protein levels and improves intensive care unit outcome.MethodsBlood samples were collected from patients with acute lung injury with 48 h of onset of acute lung injury (day 0), day 3, and day 7. Patients were given placebo or 80 mg simvastatin for up to 14 days. Plasma heparin-binding protein levels from patients with acute lung injury and healthy volunteers were measured by ELISA.ResultsLevels of plasma heparin-binding protein were significantly higher in patients with acute lung injury than healthy volunteers on day 0 (p = 0.011). Simvastatin 80 mg administered enterally for 14 days reduced plasma level of heparin-binding protein in patients. Reduced heparin-binding protein was associated with improved intensive care unit survival.ConclusionsA reduction in heparin-binding protein with simvastatin is a potential mechanism by which the statin may modify outcome from acute lung injury.Trial registrationCurrent controlled trials: ISRCTN70127774
Highlights
Heparin-binding protein is released by neutrophils during inflammation and disrupts the integrity of the alveolar and capillary endothelial barrier implicated in the development of acute lung injury and systemic organ failure
heparin-binding protein (HBP) is increased in plasma at onset of Acute lung injury (ALI) HBP concentration in plasma in healthy volunteers and patients with ALI were measured at enrollment
HBP levels and Intensive Care Unit mortality We tested whether levels of HBP correlated with ICU mortality
Summary
Heparin-binding protein is released by neutrophils during inflammation and disrupts the integrity of the alveolar and capillary endothelial barrier implicated in the development of acute lung injury and systemic organ failure. We sought to investigate whether oral administration of simvastatin to patients with acute lung injury reduces plasma heparin-binding protein levels and improves intensive care unit outcome. Acute lung injury (ALI), and its most severe form, the adult respiratory distress syndrome (ARDS) are inflammatory disorders which are commonly caused by the systemic release of cytokines and pro-inflammatory molecules [1]. ALI is characterized by alveolar epithelial and capillary endothelial barrier damage, resulting in exudation of protein-rich oedema fluid into the alveolar space, which causes functional impairment of the gas exchange [1]. There is a correlation between the number of neutrophils
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