Simvastatin decreases the level of heparin-binding protein in patients with acute lung injury

BMC Pulm Med. 2013 Jul 19:13:47. doi: 10.1186/1471-2466-13-47.

Abstract

Background: 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.

Methods: Blood 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.

Results: Levels 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.

Conclusions: A reduction in heparin-binding protein with simvastatin is a potential mechanism by which the statin may modify outcome from acute lung injury.

Trial registration: Current controlled trials: ISRCTN70127774.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / blood*
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / mortality
  • Administration, Oral
  • Adult
  • Aged
  • Antimicrobial Cationic Peptides / blood*
  • Antimicrobial Cationic Peptides / drug effects
  • Blood Proteins / drug effects
  • Carrier Proteins / blood*
  • Carrier Proteins / drug effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Intensive Care Units
  • Male
  • Middle Aged
  • Prospective Studies
  • Simvastatin / administration & dosage
  • Simvastatin / pharmacology
  • Simvastatin / therapeutic use*
  • Survival Rate
  • Treatment Outcome

Substances

  • AZU1 protein, human
  • Antimicrobial Cationic Peptides
  • Blood Proteins
  • Carrier Proteins
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Simvastatin

Associated data

  • ISRCTN/ISRCTN70127774