Abstract
Introduction: Oxidative stress and reactive oxygen species (ROS) are implicated in influenza A virus-induced lung inflammation and damage. Current therapies primarily target viral infection and replication, with little attention directed at the host immune response. The antioxidant enzyme glutathione peroxidase-1 (GPx-1) has a protective role against various diseases involving ROS.
Aim: To study the role of GPx-1 in influenza A virus-induced lung inflammation.
Methods: Male WT (C57BL/6) and GPx-1-/-mice were infected with 1×104 PFU of HKx31 (H3N2) influenza A virus. Viral titre, BALF and lung inflammation, body weight, pro-inflammatory chemokine (MIP-1α, MIP-2, KC) and protease (MMP-9) expression were assessed 3 and 7 days post infection.
Results: WT mice infected with HKx31 had significantly more BALF total cells, macrophages, neutrophils and lymphocytes at day 3 and 7 than naïve WT animals (n=5-8, P<0.05). However, GPx-1-/- mice infected with HKx31 had significantly more BALF total cells and neutrophils than infected WT mice (P<0.05). Viral titre was significantly reduced in GPx-1-/- mice at day 3 compared to WT mice (P<0.05). Infected GPx-1-/- mice lost similar amounts of weight to infected WT mice. Gene expression analysis revealed that GPx-1-/- mice had more whole lung MIP-1α, KC and MIP-2 than WT mice at day 3 and 7. Infected GPx-1-/- mice had more active MMP-9 protease in BALF and greater peribronchial inflammation and bronchial inflammatory cell exudates than infected WT mice.
Conclusions: These data indicate that GPx-1 reduces some aspects of influenza A virus-induced lung inflammation, which may improve overall outcomes of influenza infection.
- © 2011 ERS