Simvastatin inhibits smoke-induced airway epithelial injury

Implications for COPD therapy

Benjamin B. Davis, Amir Zeki, Jennifer M. Bratt, Lei Wang, Simone Filosto, William F. Walby, Nicholas Kenyon, Tzipora Goldkorn, Edward S Schelegle, Kent E Pinkerton

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death. The statin drugs may have therapeutic potential in respiratory diseases such as COPD, but whether they prevent bronchial epithelial injury is unknown. We hypothesised that simvastatin attenuates acute tobacco smokeinduced neutrophilic lung inflammation and airway epithelial injury. Spontaneously hypertensive rats were given simvastatin (20 mg·kg-1 i.p.) daily for either 7 days prior to tobacco smoke exposure and during 3 days of smoke exposure, or only during tobacco smoke exposure. Pretreatment with simvastatin prior to and continued throughout smoke exposure reduced the total influx of leukocytes, neutrophils and macrophages into the lung and airways. Simvastatin attenuated tobacco smoke-induced cellular infiltration into lung parenchymal and airway subepithelial and interstitial spaces. 1 week of simvastatin pretreatment almost completely prevented smoke-induced denudation of the airway epithelial layer, while simvastatin given only concurrently with the smoke exposure had no effect. Simvastatin may be a novel adjunctive therapy for smoke-induced lung diseases, such as COPD. Given the need for statin pretreatment there may be a critical process of conditioning that is necessary for statins' anti-inflammatory effects. Future work is needed to elucidate the mechanisms of this statin protective effect.

Original languageEnglish (US)
Pages (from-to)350-361
Number of pages12
JournalEuropean Respiratory Journal
Volume42
Issue number2
DOIs
StatePublished - Aug 1 2013

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Simvastatin
Smoke
Chronic Obstructive Pulmonary Disease
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Wounds and Injuries
Tobacco
Therapeutics
Lung
Inbred SHR Rats
Lung Diseases
Cause of Death
Pneumonia
Neutrophils
Leukocytes
Anti-Inflammatory Agents
Macrophages

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

Cite this

Simvastatin inhibits smoke-induced airway epithelial injury : Implications for COPD therapy. / Davis, Benjamin B.; Zeki, Amir; Bratt, Jennifer M.; Wang, Lei; Filosto, Simone; Walby, William F.; Kenyon, Nicholas; Goldkorn, Tzipora; Schelegle, Edward S; Pinkerton, Kent E.

In: European Respiratory Journal, Vol. 42, No. 2, 01.08.2013, p. 350-361.

Research output: Contribution to journalArticle

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