Abstract
Respiratory syncytial virus (RSV) is the leading cause of bronchiolitis in infants and young children. Although some clinical studies have speculated that tumor necrosis factor (TNF)-α is a major contributor of RSV-mediated airway disease, experimental evidence remains unclear or conflicting. TNF-α initiates inflammation and cell death through two distinct receptors: TNF-receptor (TNFR)1 and TNFR2. Here we delineate the function of TNF-α by short-lasting blockade of either receptor in an experimental BALB/c mouse model of RSV infection. We demonstrate that antibody-mediated blockade of TNFR1, but not TNFR2, results in significantly improved clinical disease and bronchoconstriction as well as significant reductions of several inflammatory cytokines and chemokines, including IL-1α, IL-1β, IL-6, Ccl3, Ccl4, and Ccl5. Additionally, TNFR1 blockade was found to significantly reduce neutrophil number and activation status, consistent with the concomitant reduction of pro-neutrophilic chemokines Cxcl1 and Cxcl2. Similar protective activity was also observed when a single-dose of TNFR1 blockade was administered to mice following RSV inoculation, although this treatment resulted in improved alveolar macrophage survival rather than reduced neutrophil activation. Importantly, short-lasting blockade of TNFR1 did not affect RSV peak replication in the lung. This study suggests a potential therapeutic approach for RSV bronchiolitis based on selective blockade of TNFR1.
Highlights
Respiratory syncytial virus (RSV) is a negative-sense single stranded RNA virus of the familyPneumoviridae [1]
Our study suggests a potential therapeutic approach for RSV bronchiolitis based on selective blockade of TNFR1
The dose of 160 μg anti-TNFR2 was associated with mortality occuring at day four in two of the three RSV-infected mice
Summary
Respiratory syncytial virus (RSV) is a negative-sense single stranded RNA virus of the familyPneumoviridae [1]. The genome of RSV encodes eleven viral proteins, including two surface glycoproteins (RSV F and RSV G). Utilizing these proteins, RSV is able to invade the epithelial lining of the nasopharynx with severe cases progressing down to the small conductive airways resulting in acute bronchiolitis [3]. RSV is able to invade the epithelial lining of the nasopharynx with severe cases progressing down to the small conductive airways resulting in acute bronchiolitis [3] This involves occlusion of the bronchiolar airways due to excessive inflammation and mucus secretion, necrosis of the bronchiolar epithelium, and peribronchiolar infiltration by various leukocytes [4,5]. Several longitudinal studies have linked RSV bronchiolitis to a heightened risk of recurrent wheezing and asthma within the first
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
