Perflubron reduces lung inflammation in respiratory syncytial virus infection by inhibiting chemokine expression and nuclear factor-kappa B activation.
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-kappa 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 alpha, MIP-1 beta, 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-kappa 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.
Haeberle
Helene A
HA
Department of Pediatrics, University of Texas Medical Branch, Galveston, Texas 77555-0369, USA.
Nesti
Frances
F
Dieterich
Hans-Juergen
HJ
Gatalica
Zoran
Z
Garofalo
Roberto P
RP
D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D018946:Chemokine CCL5 / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005466:Fluorocarbons / Q000494:pharmacology*; D006842:Hydrocarbons, Brominated; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000187:drug effects* / Q000276:immunology; D011024:Pneumonia, Viral / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis*; D011897:Random Allocation; D012016:Reference Values; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000276:immunology; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000473:pathology / Q000821:virology; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric
D018946:Chemokine CCL5; D005466:Fluorocarbons; D006842:Hydrocarbons, Brominated; D016328:NF-kappa B; D012333:RNA, Messenger; C003072:perflubron