IFN‐alpha plays a moderate role in the host response to influenza in aged treadmill‐exercised mice

IFNα is an anti‐viral protein known for its immune‐modulating involvement in influenza infection. Previous work by our lab has shown that in BALB/c mice exercise training prior to influenza infection results in improvements in illness severity in comparison to non‐exercised mice. It is possible that the exercise‐associated improvements to influenza are mediated by IFNα. To test this hypothesis, mice were treadmill‐trained for 10 weeks, and infected with Influenza (A/PR/8/34) ~24 hours after the last exercise session. Anti‐IFNα antibody or irrelevant antibody was administered 24 hours prior to infection, and continued daily through the first 4 days of infection. On day 8 post‐infection, blood, bronchoalveolar lavage (BAL) fluid, and lung draining lymph nodes were collected to assess the immune response. The results showed that exercise treatment attenuated body weight loss, increased IFNγ, IL‐10, CD8+ cells and inflammatory monocytes in the BAL of the exercised mice whether they were treated with anti‐IFNα or not. The anti‐IFNα treatment had no effect on lung viral titer, but reduced BAL IL‐5 and IL‐15. Alternatively, anti‐IFNα treatment increased BAL IFNγ and IL‐12p70, along with lymph node CD19+ and CD11c+ cells. Serum anti‐influenza IgG and IgG1 were significantly elevated with anti‐IFNα in both exercised and non‐exercised mice, and exercise treatment reduced IgG and IgG1. The results generally suggest that the majority of exercise‐associated alterations to the host defense to influenza are not mediated by IFNα however it does appear that increased TNFα and monocytes in the BAL of exercised mice maybe regulated by IFNα. Overall, this study shows that IFNα modulates the immune response in an alternative way than initially anticipated, perhaps via TNFα/iNOS producing DCs infiltrating the lungs, however this would require further investigation before a conclusion could be drawn.