ArticleCritical care (London, England)2013
Inhibition of the inflammatory cytokine tumor necrosis factor-alpha with etanercept provides protection against lethal H1N1 influenza infection in mice.
Article in Critical care (London, England), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 106 citations in OpenAlex.
- Divergent effects of tumor necrosis factor (TNF) in sepsis: a meta-analysis of experimental studies.Critical care (London, England) · 2024Pooled it
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- Peripheral blood cytokine expression levels and their clinical significance in children with influenza.Translational pediatrics · 2025Article
- The immune receptors TLR4 and SLAMF1 regulate TNF release by human metapneumovirus in human macrophages.Frontiers in immunology · 2025Article
- miR-126a-5p inhibits H1N1-induced inflammation and matrix protease secretion in lung fibroblasts by targeting ADAMTS-4.Archives of virology · 2024Article
- Meeting the Challenge of Controlling Viral Immunopathology.International journal of molecular sciences · 2024Review
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- Myeloid autophagy genes protect mice against fatal TNF- and LPS-induced cytokine storm syndromes.Autophagy · 2023Article
- In Vitro Antiviral and Anti-Inflammatory Activities ofInternational journal of molecular sciences · 2023Article
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- Controlling viral inflammatory lesions by rebalancing immune response patterns.Frontiers in immunology · 2023Review
- 5-Methoxyflavone-induced AMPKα activation inhibits NF-κB and P38 MAPK signaling to attenuate influenza A virus-mediated inflammation and lung injury in vitro and in vivo.Cellular & molecular biology letters · 2022Article
- Liver-Targeted Nanoparticles Facilitate the Bioavailability and Anti-HBV Efficacy of Baicalin In Vitro and In Vivo.Biomedicines · 2022Article
- CD33 is downregulated by influenza virus H1N1pdm09 and induces ROS and the TNF-α, IL-1β, and IL-6 cytokines in human mononuclear cells.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2022Article
- Targeting ectromelia virus and TNF/NF-κB or STAT3 signaling for effective treatment of viral pneumonia.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Autophagy and Exosome Coordinately Enhance Macrophage M1 Polarization and Recruitment in Influenza A Virus Infection.Frontiers in immunology · 2022Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionFactors implicated in influenza-mediated morbidity and mortality include robust cytokine production (cytokine storm), excessive inflammatory infiltrates, and virus-induced tissue destruction. Tumor necrosis factor-alpha (TNF-α) is an important pro-inflammatory cytokine present during influenza infection, but it is unclear whether direct inhibition of TNF-α can elicit protection against influenza infection.
methodsIn this study, the commercially available TNF-α inhibitor etanercept was used to inhibit TNF-α induced by lethal A/FM/1/47 (H1N1) influenza virus infection of mice. The effects of TNF-α inhibition on mouse survival, pathologic changes, immune cell infiltration, inflammatory cytokine secretion, Toll-like receptor expression, and activation of the NF-κB (nuclear factor kappa B) signaling pathway were evaluated.
resultsThe intranasal delivery of etanercept provided significant protection against mortality (30% of mice survived up to 14 days after infection) in mice treated with etanercept. In contrast, no survivors were found beyond 6 days in mice treated with saline after lethal challenge with H1N1 influenza virus. It was observed that etanercept significantly reduced inflammatory cell infiltration (for example, macrophages and neutrophils), inflammatory cytokine secretion (for example, interleukin-6, TNF-α, and interferon gamma), and expression of Toll-like receptors (TLR-3, TLR-4, and TLR-7). Etanercept also downregulated and inhibited the cascade proteins of the NF-κB signaling pathway (for example, MyD88, TRIF, NF-κB, and p65), as well as enhanced host control of virus replication.
conclusionsThese findings indicate that etanercept, by blocking TNF-α, can significantly downregulate excessive inflammatory immune responses and provide protection against lethal influenza infection, making its use a novel strategy for controlling severe influenza-induced viral pneumonia.
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