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Published ahead of print on September 28, 2006, doi:10.1164/rccm.200603-319OC

Am. J. Respir. Crit. Care Med., Volume 174, Number 12, December 2006, 1361-1369

A more recent version of this article appeared on December 15, 2006
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Submitted on March 3, 2006
Accepted on September 28, 2006

Antioxidant Treatment Ameliorates Respiratory Syncytial Virus-Induced Disease and Lung Inflammation

Shawn Monique Castro1, Antonieta Guerrero-Plata2, Giovanni Suarez-Real2, Patrick A Adegboyega3, Giuseppe N Colasurdo4, Amir M Khan4, Roberto P Garofalo5, and Antonella Casola5*

1 Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA; Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, Texas, USA, 2 Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA, 3 Department of Pathology, University of Texas Medical Branch, Galveston, Texas, USA, 4 Department of Pediatrics, University of Texas Health Science Center, Houston, Texas, USA, 5 Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas, USA; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas, USA; Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, Texas, USA

* To whom correspondence should be addressed. E-mail: ancasola{at}utmb.edu.

Rationale: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection in children. No treatment has been shown to significantly improve the clinical outcome of patients with this infection. Recent evidence suggests that oxidative stress could play an important role in the pathogenesis of acute and chronic lung inflammatory diseases. We do not known whether RSV induces pulmonary oxidative stress and whether antioxidant treatment can modulate RSV-induced lung disease. Objectives: To investigate the effect of antioxidant administration on RSV-induced lung inflammation, clinical disease and airway hyperreactivity (AHR). Methods: BALB/c mice were infected with 107 PFU of RSV, in the presence or absence of orally administered butylated hydroxyanisole (BHA), an antioxidant. Malondialdehyde (MDA) and 4-hydroxynonenal (HNE) were measured in bronchoalveoar lavages (BALs) by colorimetric assay. Cytokine and chemokines were measured in BAL by Bioplex and leukotrienes were measure by enzyme-linked immunosorbent assay. AHR to metacholine was measured by whole-body plethysmography. Results: BHA treatment significantly attenuated RSV-induced lung oxidative stress, as indicated by the decrease of MDA and 4-HNE content in BAL of RSV-infected mice. RSV-induced clinical illness and body weight loss were also reduced by BHA treatment, which inhibited neutrophil recruitment to the lung and significantly reduced pulmonary cytokine and chemokine production, following RSV infection. Similarly, antioxidant treatment attenuated RSV-induced airway hyperreactivity. Conclusion: Modulation of oxidative stress represents a potential novel pharmacological approach to ameliorate RSV-induced acute lung inflammation and potentially prevent long-term consequences associated with RSV infection, such as bronchial asthma.
Key words: RSV, lung inflammation, chemokines, oxidative stress, antioxidant




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