Statins reduce ambient particulate matter-induced lung inflammation by promoting the clearance of particulate matter, < 10 μm from lung tissues.

TitleStatins reduce ambient particulate matter-induced lung inflammation by promoting the clearance of particulate matter, < 10 μm from lung tissues.
Publication TypeJournal Article
Year of Publication2013
AuthorsMiyata, R, Bai, N, Vincent, R, Sin, DD, van Eeden, SF
JournalChest
Volume143
Issue2
Pagination452-60
Date Published2013 Feb 1
ISSN1931-3543
KeywordsAnimals, Bronchoalveolar Lavage Fluid, Cell Movement, Disease Models, Animal, Female, Hydroxymethylglutaryl-CoA Reductase Inhibitors, In Vitro Techniques, Interleukin-6, Interleukin-8, Lovastatin, Lung, Macrophages, Alveolar, Neutrophils, Particulate Matter, Phagocytosis, Pneumonia, Rabbits
Abstract

BACKGROUND: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) suppress ambient particulate matter, 10 μm (PM(10) )-induced inflammatory response in vitro. The aim of this study was to determine the effect of statins on PM(10) -induced lung inflammation in vivo.

METHODS: New Zealand white rabbits were exposed to either PM(10) (1.0 mg/kg) or saline by direct intratracheal instillation three times a week for 4 weeks lovastatin 5.0 mg/kg/d. BAL fluid was assessed for cell counts and proinflammatory cytokine levels. Lung inflammation was quantified using immunohistochemical techniques and morphometric methods. Ex vivo phagocytosis assay of alveolar macrophages using PM 10 particles was performed. Distribution of PM(10) particles in lung tissues and draining lymph nodes was quantified morphometrically to evaluate the clearance of PM(10) particles.

RESULTS: PM(10) exposure increased the production of IL-6 and IL-8, promoted the recruitment of macrophages and polymorphonuclear leukocytes into the lung, and activated these recruited leukocytes. Lovastatin significantly suppressed all these effects. Lovastatin increased the phagocytic activity of macrophages and promoted the migration of PM 10 -laden macrophages to the regional lymph nodes.

CONCLUSIONS: Lovastatin attenuates the PM(10) -induced recruitment and activation of alveolar macrophages and polymorphonuclear leukocytes, reduces local proinflammatory cytokine production, and promotes the clearance of PM(10) particles from lung tissues to regional lymph nodes. These novel pleiotropic properties of statins are most likely to contribute to the downregulation of PM(10) -induced lung inflammation.

DOI10.1378/chest.12-1237
Alternate JournalChest
PubMed ID22910717
Grant List / / Canadian Institutes of Health Research / Canada