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Original Research: Occupational and Environmental Lung Diseases |

Statins Reduce Ambient Particulate Matter-Induced Lung Inflammation by Promoting the Clearance of Particulate Matter < 10 μm From Lung TissuesStatins Reduce PM10-Induced Lung Inflammation

Ryohei Miyata, MD, PhD; Ni Bai, PhD; Renaud Vincent, PhD; Don D. Sin, MD, MPH, FCCP; Stephan F. Van Eeden, MD, PhD
Author and Funding Information

From the UBC James Hogg Research Centre (Drs Miyata, Bai, Sin, and Van Eeden), Institute for Heart + Lung Health, St. Paul’s Hospital, The University of British Columbia, Vancouver, BC; Department of Anesthesiology, Pharmacology and Therapeutics (Dr Bai), The University of British Columbia, Vancouver, BC; and Environmental Health, Science and Research Bureau (Dr Vincent), Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada.

Correspondence to: Stephan F. Van Eeden, MD, PhD, UBC James Hogg Research Centre, Institute for Heart + Lung Health, St. Paul’s Hospital, The University of British Columbia, Room 166, 1081 Burrard St, Vancouver, BC V6Z 1Y6, Canada; e-mail: Stephan.vanEeden@hli.ubc.ca


Funding/Support: This study was supported by operating grants from the Heart and Stroke Foundation of Canada, Michael Smith Foundation for Health Research, and the Canadian Institutes of Health Research.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2013;143(2):452-460. doi:10.1378/chest.12-1237
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Background:  The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) suppress ambient particulate matter < 10 μm (PM10)-induced inflammatory response in vitro. The aim of this study was to determine the effect of statins on PM10-induced lung inflammation in vivo.

Methods:  New Zealand white rabbits were exposed to either PM10 (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 PM10 particles was performed. Distribution of PM10 particles in lung tissues and draining lymph nodes was quantified morphometrically to evaluate the clearance of PM10 particles.

Results:  PM10 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 PM10-laden macrophages to the regional lymph nodes.

Conclusions:  Lovastatin attenuates the PM10-induced recruitment and activation of alveolar macrophages and polymorphonuclear leukocytes, reduces local proinflammatory cytokine production, and promotes the clearance of PM10 particles from lung tissues to regional lymph nodes. These novel pleiotropic properties of statins are most likely to contribute to the downregulation of PM10-induced lung inflammation.

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