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Perflubron Reduces Lung Inflammation in Respiratory Syncytial Virus Infection by Inhibiting Chemokine Expression and Nuclear Factor–B Activation

Departments of Pediatrics, Pathology, Microbiology, and Immunology, University of Texas Medical Branch, Galveston, Texas; and Department of Anesthesiology, University Hospital, Tuebingen, Germany

Correspondence and requests for reprints should be addressed to Roberto P. Garofalo, M.D., Dept. of Pediatrics, Division of Immunology/Allergy/Rheumatology, University of Texas Medical Branch of Galveston, 301 University Boulevard, Galveston, TX 77555-0369. E-mail: rpgarofa{at}utmb.edu

Airway mucosa inflammation plays a critical role in the pathogenesis of lower respiratory tract infections caused by respiratory syncytial virus (RSV), the major etiologic agent of bronchiolitis in infancy. Type and intensity of cellular infiltration are dictated by inflammatory chemokines, which are rapidly and abundantly induced in lung tissue by RSV. This process is, to a large extent, transcriptionally regulated by RSV-mediated activation of the nuclear factor–B. The administration of a perfluorocarbon (PFC) liquid, such as perflubron, during partial liquid ventilation improves lung function and also reduces inflammation. In this study we demonstrate that treatment of BALB/c mice with perflubron intranasally 6 hours after RSV infection significantly inhibited lung cellular inflammation as well as the expression of the chemokines RANTES, MIP-1, MIP-1ß, and MIP-2, compared with phosphate-buffered saline–treated control mice. However, perflubron treatment did not affect RSV replication. Strikingly, treatment with perflubron abrogated nuclear factor–B activation in lung of RSV-infected mice. These results demonstrate a novel mechanism by which PFC may exert antiinflammatory activity and suggest that partial liquid ventilation with PFC may be considered in future clinical trials for infants with severe RSV infections requiring mechanical ventilation.

Key Words: respiratory syncytial virus • perflubron • nuclear factor–B • inflammation • chemokines

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