Role of oxidative stress on diesel-enhanced influenza infection in mice
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 articleSubject
respiratory syncytial virusexhaust particle chemicals
ambient
particulate matter
airway epithelial-cells
inflammatory responses
united-states
listeria-monocytogenes
engine emissions
il-4
production
term exposure
toxicology
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https://hdl.handle.net/10161/4378Published Version (Please cite this version)
10.1186/1743-8977-7-34Citation
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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