Statins reduce ambient particulate matter-induced lung inflammation by promoting the clearance of particulate matter, < 10 μm from lung tissues.
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.
UBC James Hogg Research Centre, Institute for Heart + Lung Health, St. Paul's Hospital, The University of British Columbia, Vancouver, BC.
Ryohei
R
Miyata
UBC James Hogg Research Centre, Institute for Heart + Lung Health, St. Paul's Hospital, The University of British Columbia, Vancouver, BC; Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Vancouver, BC.
Ni
N
Bai
Environmental Health, Science and Research Bureau, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, ON, Canada.
Renaud
R
Vincent
UBC James Hogg Research Centre, Institute for Heart + Lung Health, St. Paul's Hospital, The University of British Columbia, Vancouver, BC.
Don D
DD
Sin
UBC James Hogg Research Centre, Institute for Heart + Lung Health, St. Paul's Hospital, The University of British Columbia, Vancouver, BC. Electronic address: Stephan.vanEeden@hli.ubc.ca.
Stephan F
SF
Van Eeden
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D066298:In Vitro Techniques; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016676:Macrophages, Alveolar / Q000473:pathology / Q000502:physiology; D009504:Neutrophils / Q000473:pathology / Q000502:physiology; D052638:Particulate Matter / Q000009:adverse effects*; D010587:Phagocytosis / Q000187:drug effects / Q000502:physiology*; D011014:Pneumonia / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control*; D011817:Rabbits
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D015850:Interleukin-6; D016209:Interleukin-8; D052638:Particulate Matter; D008148:Lovastatin