Tumor Necrosis Factor Alpha Exerts Powerful Anti-Influenza Virus Effects in Lung Epithelial Cells
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Previous studies have associated influenza virus-induced expression of inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), with influenza pathogenesis in the human respiratory tract and have suggested that alpha and beta interferons are the first cytokines recruited to counteract such infection. However, we report here that TNF-α has powerful anti-influenza virus activity. When infected with influenza virus, cultured porcine lung epithelial cells expressed TNF-α in a dose-dependent manner. Expression of TNF-α was induced only by replicating virus. TNF-α showed strong antiviral activity against avian, swine, and human influenza viruses, and the antiviral effect of TNF-α was greater than that of gamma or alpha interferon. These findings suggest that TNF-α serves as the first line of defense against influenza virus infection in the natural host.
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Secondary effects of cytokine cascades, as opposed to the direct effect of the virus, in amplifying and broadening the proinflammatory response may be important in the escalation of cytokine storm.
“The concept of secondary effects of cytokine cascades, as opposed to the direct effect of the virus, in amplifying and broadening the proinflammatory response may be important in the escalation of cytokine storm (24,111,125).”
From Into the Eye of the Cytokine Storm (2012) · cites this paper as [125]
TNF is highly expressed across infection models, including primary human respiratory epithelial cells and human monocyte-derived macrophages, compared with seasonal H1N1 and swine-origin H1N1 influenza virus infection.
“It is highly expressed across infection models, including primary human respiratory epithelial cells (24, 125) and human monocyte-derived macrophages (26, 59, 62), compared with during seasonal H1N1 influenza virus and swine-origin H1N1 influenza virus (SOIV) infection (111).”
From Into the Eye of the Cytokine Storm (2012) · cites this paper as [125]
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- Authors
- Seo, S. H., & Webster, R. G.
- Affiliations
- St. Jude Children's Research Hospital (US)
- Venue
- Journal of Virology
- Publisher
- American Society for Microbiology
- Published
- 2002-02
- Volume
- 76
- Issue
- 3
- Pages
- 1071-1076
- ISSN
- 0022-538X (ISSN-L)
- 1098-5514
- PMC
- PMC135862
- OpenAlex
- W2107705757
- Cited by
- 275
- References
- 50
- Citations by year
- 2026: 7 · 2025: 12 · 2024: 19 · 2023: 18 · 2022: 18 · 2021: 24 · 2020: 22 · 2019: 9 · 2018: 9 · 2017: 10 · 2016: 14 · 2015: 10 · 2014: 13 · 2013: 7 · 2012: 5
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Lebanese Syrian Associated Charities (CA 21765)
- National Cancer Institute (CA21765, P30CA021765)
- National Institute of Allergy and Infectious Diseases (AI795357, AI-29860)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Health Sciences › Medicine › Epidemiology › Respiratory viral infections research
- Keywords
- TNF-α, influenza virus, antiviral activity, lung epithelial cells, interferon, innate immunity, swine influenza, avian influenza, human influenza, cytokine expression, respiratory infections
- MeSH terms
- Animals, Antiviral Agents, Cell Line, Chick Embryo, Humans, Interferon-gamma, Influenza A virus, Influenza B virus, Swine, Tumor Necrosis Factor-alpha, Virus Replication, Gene Expression, Interferon-alpha, Interferon-beta
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