Respiratory syncytial virus infection reduces lung inflammation and fibrosis in mice exposed to vanadium pentoxide

BACKGROUND: Vanadium pentoxide (V(2)O(5)) exposure is a cause of occupational bronchitis and airway fibrosis. Respiratory syncytial virus (RSV) is a ubiquitous pathogen that causes airway inflammation. It is unknown whether individuals with pre-existing respiratory viral infection are susceptible to V(2)O(5)-induced bronchitis. We hypothesized that respiratory viral infection will exacerbate vanadium-induced lung fibrosis. METHODS: In this study we investigated the effect of RSV pre- or post-exposure to V(2)O(5 )in male AKR mice. Mice were pre-exposed by intranasal aspiration to RSV or media vehicle prior to intranasal aspiration of V(2)O(5 )or saline vehicle at day 1 or day 7. A parallel group of mice were treated first with V(2)O(5 )or saline vehicle at day 1 and day 7 then post-exposed to RSV or media vehicle at day 8. RESULTS: V(2)O(5)-induced airway inflammation and fibrosis were decreased by RSV pre- or post-exposure. Real time quantitative RT-PCR showed that V(2)O(5 )significantly increased lung mRNAs encoding pro-fibrogenic growth factors (TGF-β1, CTGF, PDGF-C) and collagen (Col1A2), but also increased mRNAs encoding anti-fibrogenic type I interferons (IFN-α, -β) and IFN-inducible chemokines (CXCL9 and CXCL10). RSV pre- or post-exposure caused a significantly reduced mRNAs of pro-fibrogenic growth factors and collagen, yet reduced RNA levels of anti-fibrogenic interferons and CXC chemokines. CONCLUSIONS: Collectively these data suggest that RSV infection reduces the severity of V(2)O(5)-induced fibrosis by suppressing growth factors and collagen genes. However, RSV suppression of V(2)O(5)-induced IFNs and IFN-inducible chemokines suggests that viral infection also suppresses the innate immune response that normally serves to resolve V(2)O(5)-induced fibrosis.