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Role of oxidative stress on diesel-enhanced influenza infection in mice

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Date
2010
Authors
Gowdy, Kymberly M
Krantz, Quentin T
King, Charly
Boykin, Elizabeth
Jaspers, Ilona
Linak, William P
Gilmour, M Ian
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Abstract
Numerous studies have shown that air pollutants, including diesel exhaust (DE), reduce host defenses, resulting in decreased resistance to respiratory infections. This study sought to determine if DE exposure could affect the severity of an ongoing influenza infection in mice, and examine if this could be modulated with antioxidants. BALB/c mice were treated by oropharyngeal aspiration with 50 plaque forming units of influenza A/HongKong/8/68 and immediately exposed to air or 0.5 mg/m(3) DE (4 hrs/day, 14 days). Mice were necropsied on days 1, 4, 8 and 14 post-infection and lungs were assessed for virus titers, lung inflammation, immune cytokine expression and pulmonary responsiveness (PR) to inhaled methacholine. Exposure to DE during the course of infection caused an increase in viral titers at days 4 and 8 post-infection, which was associated with increased neutrophils and protein in the BAL, and an early increase in PR. Increased virus load was not caused by decreased interferon levels, since IFN-beta levels were enhanced in these mice. Expression and production of IL-4 was significantly increased on day 1 and 4 p.i. while expression of the Th1 cytokines, IFN-gamma and IL-12p40 was decreased. Treatment with the antioxidant N-acetylcysteine did not affect diesel-enhanced virus titers but blocked the DE-induced changes in cytokine profiles and lung inflammation. We conclude that exposure to DE during an influenza infection polarizes the local immune responses to an IL-4 dominated profile in association with increased viral disease, and some aspects of this effect can be reversed with antioxidants.
Type
Other article
Subject
respiratory syncytial virus
exhaust particle chemicals
ambient
particulate matter
airway epithelial-cells
inflammatory responses
united-states
listeria-monocytogenes
engine emissions
il-4
production
term exposure
toxicology
Permalink
https://hdl.handle.net/10161/4378
Published Version (Please cite this version)
10.1186/1743-8977-7-34
Citation
Gowdy,Kymberly M.;Krantz,Quentin T.;King,Charly;Boykin,Elizabeth;Jaspers,Ilona;Linak,William P.;Gilmour,M. Ian. 2010. Role of oxidative stress on diesel-enhanced influenza infection in mice. Particle and Fibre Toxicology 7( ): 34-34.
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