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2619573 
Journal Article 
Abstract 
Progressive exposure to ambient fine and ultrafine particles induces a duration-dependent pattern of pro-inflammatory cytokine and chemokine expression in the lungs of mice 
Plummer, LE; Ruehl, CR; Kleeman, MJ; Pinkerton, KE 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A2808 
English 
WOS:000208771001720 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Rationale: Growing evidence suggests exposure to particulate matter is associated with increased morbidity and mortality due to cardiopulmonary complications.

Methods: Pulmonary inflammation was measured in the lungs of mice exposed to summertime fine/ultrafine concentrated ambient particles (CAPS) or to filtered air in Fresno, CA, for 6 hours a day for 3, 6, 9, or 12 days (mean concentration of 159 ± 11 µg/m^3). Levels of pro- and anti-inflammatory cytokines and chemokines were measured using a bead-based ELISA assay.

Results: Significant duration-dependent elevations in cytokine and chemokine levels were observed that were followed by significant reductions to below control levels. After three days of CAPS exposure, macrophage inflammatory protein 2 (MIP-2) was elevated (250% of control) but then fell (50% of control) after six, nine, and twelve days of exposure (p<0.05). Pro-inflammatory and TH2 cytokine, Interleukin 13 (IL-13) was significantly increased from day matched controls at three days (p<0.05) and at six days from three days. IL-13 then was significantly reduced to 100% of control values at nine and twelve days (p<0.05). Anti-inflammatory and inhibitory cytokine IL-10 levels were increased to 160% of control levels after six days followed by a significant reduction of IL-10 and IL-10 influenced cytokines, interleukin 3 (IL-3), granulocyte macrophage colony stimulating factor (GM-CSF), interferon gamma (IFN-g), and tumor necrosis factor-alpha (TNF-α). IL-3 and GM-CSF were significantly reduced from 160% of control at three days to 80% and 60% of control at nine and twelve days, respectively. IFN-γ and TNF-α were significantly reduced from 140% of control at 3 days to 100% and 80% of control for IFN-γ and to 80% and 60% of control for TNF-α at nine and twelve days, respectively. Consistent results demonstrate marked reductions from day matched controls for all measured cytokines and chemokines after twelve days of exposure. Comparisons between control and CAPS-exposed groups and exposure duration-based comparisons between exposure groups normalized to day matched filtered air control mice were made using one-way ANOVA.

Conclusions: We conclude that progressive exposure to CAPS induces unique duration-dependent changes in levels of inflammatory activity in the lungs of mice that could be influenced by fluctuations in particle mass and/or composition. Pro-inflammatory cytokine and chemokine levels peak after three and six days of CAPS exposure and are significantly reduced to below control levels after twelve days of exposure. These reductions may be influenced by anti-inflammatory effects of IL-10. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010