What question did this study set out to answer?

To evaluate the effects of IFN-β on disease outcomes in older mice infected with influenza A virus.

March 22, 2026Open Access

IFN-β as a therapeutic agent for influenza A virus infection in old mice

Key Points

To evaluate the effects of IFN-β on disease outcomes in older mice infected with influenza A virus.
Inoculated young and old male mice intranasally with H1N1 virus or saline.
Administered IFN-β to old mice before and post-infection.
Measured gene expression in the lung and brain via qRT-PCR and nCounts.
Analyzed data using nSolver 4.0 and IPA® software.
IFN-β treated old mice experienced less weight loss compared to untreated old mice.
Increased lung viral load was observed at 3 days post-infection in treated mice.
No significant changes in lung/body weight ratio or histopathological damage.
Inhibition of brain inflammatory genes was noted at 3 days post-infection with a rebound by 7 days.

Abstract

Age > 65 yrs is a risk factor for poor outcomes to influenza A virus (IAV) infection, due in part to dysregulated interferon (IFN) responses. In some models of IFN dysregulation, IFN-β administration during IAV infection improves survival and antiviral defenses. This study tested whether IFN-β administration to old mice modified disease after IAV infection without accentuating lung or brain damage. Young (12-weeks) and old (70-weeks) male C57Bl/6 J mice were inoculated intranasal (i.n.) with 200 PFU H1N1 A/PR/34/8 (PR8) or sterile saline. Old mice received IFN-β (2,000 U) i.n. 1d before and post-infection (p.i). Gene expression in lung and brain was measured by quantitative real time-PCR (qRT-PCR), 3d and 7d p.i. and by nCounts in whole brain, then analyzed with nSolver 4.0 and IPA® software. IFN-β treated old mice lost significantly less weight than did untreated old mice. IFN-β treatment increased the lung viral load at 3d p.i. without significantly changing the lung/body weight ratio, expression of lung inflammatory mediator genes, or histopathology of lung and brain. In contrast, brain inflammatory genes and pathways were inhibited at 3d p.i. by IFN-β but rebounded by 7d p.i. while damage-associated and some behavioral function pathways remained suppressed. TSPO, TNF, TREM2, and PIAS were possible upstream regulators of altered inflammatory and neurocognitive pathways. IFN-β administration to IAV-infected old mice improved overall outcome without worsening lung damage and inhibited neuroinflammatory and brain damage-associated pathways. These results suggest IFN-β warrants further investigation as adjunctive treatment for severe viral infections in select hosts.

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