title: Simvastatin inhibits smoke-induced airway epithelial injury: implications for COPD therapy.
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 smoke-induced 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.
authors.affiliation: 1Center for Health and the Environment, University of California, Davis, CA, USA.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Davis
authors.forename: Amir A
authors.initials: AA
authors.lastname: Zeki
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Bratt
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Simone
authors.initials: S
authors.lastname: Filosto
authors.forename: William F
authors.initials: WF
authors.lastname: Walby
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Kenyon
authors.forename: Tzipora
authors.initials: T
authors.lastname: Goldkorn
authors.forename: Edward S
authors.initials: ES
authors.lastname: Schelegle
authors.forename: Kent E
authors.initials: KE
authors.lastname: Pinkerton
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid; D002784:Cholesterol / Q000737:chemistry; D004848:Epithelium / Q000473:pathology*; D007249:Inflammation / Q000517:prevention & control / Q000628:therapy; D007962:Leukocytes / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000517:prevention & control* / Q000628:therapy*; D051381:Rats; D011918:Rats, Inbred SHR; D012129:Respiratory Function Tests; D019821:Simvastatin / Q000494:pharmacology*; D012906:Smoke / Q000009:adverse effects*; D016896:Treatment Outcome; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D012906:Smoke; D002784:Cholesterol; D019821:Simvastatin; D020559:Monomeric GTP-Binding Proteins; D020741:rho GTP-Binding Proteins