ArticleScientific reports2017
Rapamycin adjuvant and exacerbation of severe influenza in an experimental mouse model.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.
- Rapamycin not dietary restriction improves resilience against pathogens: a meta-analysis.GeroScience · 2023Pooled it
- Passive immune therapy and other immunomodulatory agents for the treatment of severe influenza: Systematic review and meta-analysis.Influenza and other respiratory viruses · 2020Pooled it
- Autophagy and Respiratory Viruses: Mechanisms, Viral Exploitation, and Therapeutic Insights.Cells · 2025Review
- Editorial: Community series in the regulation of the host immune activation in respiratory virus infections, volume II.Frontiers in immunology · 2025Article
- Discovery of common molecular signatures and drug repurposing for COVID-19/Asthma comorbidity: ACE2 and multi-partite networks.Cell cycle (Georgetown, Tex.) · 2024Article
- An IL-17-EGFR-TRAF4 axis contributes to the alleviation of lung inflammation in severe influenza.Communications biology · 2023Article
- Rapalogs downmodulate intrinsic immunity and promote cell entry of SARS-CoV-2.The Journal of clinical investigation · 2022Article
- Influenza antivirals and animal models.FEBS open bio · 2022Review
- Dynamically linking influenza virus infection kinetics, lung injury, inflammation, and disease severity.eLife · 2021Article
- Targeting nucleotide metabolism as the nexus of viral infections, cancer, and the immune response.Science advances · 2021Review
- Influenza Therapeutics in Clinical Practice-Challenges and Recent Advances.Cold Spring Harbor perspectives in medicine · 2021Review
- Rapamycin: Drug Repurposing in SARS-CoV-2 Infection.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Interferon-inducer antivirals: Potential candidates to combat COVID-19.International immunopharmacology · 2021Review
- Critical care management of adults with community-acquired severe respiratory viral infection.Intensive care medicine · 2020Review
- Delayed oseltamivir plus sirolimus treatment attenuates H1N1 virus-induced severe lung injury correlated with repressed NLRP3 inflammasome activation and inflammatory cell infiltration.PLoS pathogens · 2018Article
- mTOR inhibitors lower an intrinsic barrier to virus infection mediated by IFITM3.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Influenza virus infection often causes severe disease and acute respiratory distress syndrome. It is a common belief that overwhelming immune response contributes to the severe illness. Physicians and researchers have put forth immune modulation as salvage therapy for better recovery. However, empiric corticosteroid failed in both humans and animal models. Reported success with Rapamycin in humans prompted a comprehensive animal study and mechanistic dissection. Here we report the effect of Rapamycin alone or in combination with Oseltamivir for severe influenza in BALB/c mice. We found that Rapamycin had no antiviral effect against H1N1, H3N2 and novel-H1N1 influenza viruses in vitro. Rapamycin alone aggravated the severe disease of PR8 H1N1 influenza virus infection in mice. Timely Oseltamivir anti-viral therapy abolished the disease. Delayed Oseltamivir treatment could not prevent severe illness and Rapamycin adjuvant was associated with exacerbated disease. Rapamycin adjuvant suppressed influenza hemagglutinin antigen-specific T cell immunity and impaired virus clearance from the lungs. It also resulted in intensified lung pathology with increased intra-alveolar edema and hyaline deposition. Rapamycin may work as the salvage therapy for severe influenza but it is very difficult to define the appropriate window for such treatment to take effect.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.