Introduction & Aims: Patients with respiratory diseases are both more susceptible to viral infection and developing more severe symptoms. These exacerbated symptoms often lead to deleterious effects such as irreversible disease progression. Emerging evidence suggests that the elevated transforming growth factor-beta (TGF) seen in patients with respiratory disease likely plays a crucial role in suppressing the immune response. Oral pirfenidone (PFD), an anti-fibrotic used to treat patients with pulmonary fibrosis, has previously been shown to reduce TGF-enhanced viral infection. This study aimed to determine if inhaled PFD was as beneficial as oral PFD.
Methods: Transgenic C57Bl/6 mice with inducible over-expression of TGF were treated with intranasal vehicle (control), oral PFD (oPFD, 100mg/kg) or intranasal PFD (iPFD, 6.7mg/kg) daily, starting 2 days prior to infection with IAV (1x102 PFU, HKx31). At 3 days post infection, mice were culled. Tissue and bronchoalveolar lavage (BAL) were collected for assessment of infection, inflammation and immune response.
Results: oPFD afforded protection against IAV-induced weight loss (p<0.01), while both oPFD and iPFD reduced lung viral load (p<0.05) as measured by plaque assay of lung homogenates. TNFa and KC in BAL fluid were also reduced by both oPFD and iPFD (p<0.05), as measured by ELISA.
Conclusion: This study demonstrated that a 15-fold lower dose of iPFD was able to afford protection against TGF-enhanced viral infection and inflammation. These promising findings present the possibility of treating patients with respiratory disease with low dose inhaled PFD, protecting them from worse infection outcomes with fewer side effects.