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Respiratory diseases in cyclophosphamide-treated mice. II. Decreased virulence of PR8 influenza virus
Abstract:
Mice infected intranasally with the PR8 strain of influenza virus were treated with cyclophosphamide, a potent immunologic suppressor. During the first week of infection, mortality in the unmodified influenza infection averaged 65%, whereas in those animals also treated with cyclophosphamide it averaged 22.5%. After the first week, the mortality rate in the infected cyclophosphamide-treated animals rose to that seen during the first week in the animals only infected. This decreased mortality in the first week was found despite the fact that the cyclophosphamide-treated and infected animals had higher virus titers which persisted longer, decreased circulating antibody, and a decreased interferon response. This delayed mortality appeared to be related to the finding of decreased cellular infiltration in the lungs of infected cyclophosphamide-treated animals.
Insights
Cyclophosphamide treatment significantly reduced early mortality in mice infected with influenza A virus (PR8 strain). This survival benefit was linked to decreased lung cellularity, despite impaired immune responses.
Area of Science:
- Immunology
- Virology
- Pharmacology
Background:
- Influenza A virus (IAV) infection poses a significant global health threat.
- Understanding host-pathogen interactions and immune responses is crucial for developing effective treatments.
- Immunosuppressive agents can modulate disease severity and outcomes.
Purpose of the Study:
- To investigate the effect of cyclophosphamide, an immunosuppressive drug, on the mortality and immune response in a mouse model of influenza A virus infection.
- To elucidate the mechanisms underlying the observed changes in disease progression and outcome.
Main Methods:
- Intranasal inoculation of mice with the PR8 strain of influenza A virus.
- Administration of cyclophosphamide as an immunosuppressive agent.
- Monitoring of mortality rates, viral titers, antibody production, interferon response, and lung cellular infiltration.
Main Results:
- Cyclophosphamide treatment significantly decreased early-phase mortality (22.5%) compared to untreated infected mice (65%).
- Despite reduced early mortality, cyclophosphamide-treated mice exhibited higher and more persistent viral titers, reduced circulating antibodies, and a diminished interferon response.
- Delayed mortality was observed in cyclophosphamide-treated mice after the first week.
- Decreased cellular infiltration in the lungs of infected cyclophosphamide-treated mice was noted.
Conclusions:
- Early administration of cyclophosphamide confers a survival advantage during the initial phase of influenza A virus infection in mice.
- The protective effect is associated with reduced lung inflammation and cellular infiltration, rather than enhanced antiviral immunity.
- These findings suggest a complex interplay between immunosuppression, viral replication, and host inflammatory responses in determining influenza disease outcomes.