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Antioxidant Treatment Ameliorates Respiratory Syncytial Virus–induced Disease and Lung Inflammation

Departments of Pediatrics, Pharmacology and Toxicology, Pathology, Microbiology and Immunology, and Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston; and Department of Pediatrics, University of Texas Health Science Center, Houston, Texas

Correspondence and requests for reprints should be addressed to Antonella Casola, M.D., Department of Pediatrics, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-0366. 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 plaque-forming units of RSV, in the presence or absence of orally administered butylated hydroxyanisole (BHA), an antioxidant. Malondialdehyde and 4-hydroxynonenal were measured in bronchoalveoar lavage (BAL) by colorimetric assay. Cytokines and chemokines were measured in BAL by Bio-Plex and leukotrienes were measured by enzyme-linked immunosorbent assay. AHR to methacholine challenge was measured by whole-body plethysmography.

Results: BHA treatment significantly attenuated RSV-induced lung oxidative stress, as indicated by the decrease of malondialdehyde and 4-hydroxynonenal 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 after RSV infection. Similarly, antioxidant treatment attenuated RSV-induced AHR.

Conclusion: Modulation of oxidative stress represents a potential novel pharmacologic approach to ameliorate RSV-induced acute lung inflammation and potentially prevent long-term consequences associated with RSV infection, such as bronchial asthma.

Key Words: antioxidant • chemokines • lung inflammation • oxidative stress • respiratory syncytial virus

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Oxidative stress has been shown to play an important role in the pathogenesis of acute and chronic lung inflammatory diseases, such as asthma, lung fibrosis, and chronic obstructive pulmonary disease. What This Study Adds to the Field Respiratory syncytial virus induces oxidative stress in vivo. Antioxidant administration significantly reduces lung pulmonary inflammation and ameliorates clinical disease due to respiratory syncytial virus.

 

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