Role of oxidative stress on diesel-enhanced influenza infection in mice
1 Division of Pulmonary, Allergy, and Critical Care, Duke University Medical Center, 106 Research Dr., 2100B MSRB2, Durham, NC 27710, USA
2 Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, United States Environmental Protection Agency, 109 T.W. Alexander Dr., RTP, NC, 27711, USA
3 Air Pollution Prevention and Control Division, National Risk Management Research Laboratory, United States Environmental Protection Agency, 109 T.W. Alexander Dr., RTP, NC 27711, USA
4 Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, 104 Mason Farm Rd, CB 7310, Chapel Hill, NC 27599, USA
5 Department of Pediatrics, University of North Carolina, 104 Mason Farm Rd, CB 7310, Chapel Hill, NC 27599, USA
Particle and Fibre Toxicology 2010, 7:34 doi:10.1186/1743-8977-7-34Published: 22 November 2010
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/m3 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-β 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-γ 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.