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Targeting tumour necrosis factor to ameliorate viral pneumonia


Pandey, P and Karupiah, G, Targeting tumour necrosis factor to ameliorate viral pneumonia, The FEBS Journal pp. 1-18. ISSN 1742-464X (2021) [Substantial Review]

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DOI: doi:10.1111/febs.15782


Pneumonia is a serious complication associated with inflammation of the lungs due to infection with viral pathogens. Seasonal and pandemic influenza viruses, variola virus (agent of smallpox) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; agent of COVID-19) are some leading examples. Viral pneumonia is triggered by excessive inflammation associated with dysregulated cytokine production, termed ‘cytokine storm’. Several cytokines have been implicated but tumour necrosis factor (TNF) plays a critical role in driving lung inflammation, severe lung pathology and death. Despite this, the exact role TNF plays in the aetiology and pathogenesis of virus infection-induced respiratory complications is not well understood. In this review, we discuss the pathological and immunomodulatory roles of TNF in contributing to immunopathology and resolution of lung inflammation, respectively, in mouse models of influenza- and smallpox (mousepox)-induced pneumonia. We review studies that have investigated dampening of inflammation on the outcome of severe influenza and orthopoxvirus infections. Most studies on the influenza model have evaluated the efficacy of treatment with anti-inflammatory drugs, including anti-TNF agents, in animal models on the day of viral infection. We question the merits of those studies as they are not transferable to the clinic given that individuals generally present at a hospital only after the onset of disease symptoms and not on the day of infection. We propose that research should be directed at determining whether dampening lung inflammation after the onset of disease symptoms will reduce morbidity and mortality. Such a treatment strategy will be more relevant clinically.

Item Details

Item Type:Substantial Review
Keywords:anti-inflammatory drugs, anti-TNF therapeutics, antiviral and anti-inflammatory drug combination therapy, antivirals, dysregulated lung inflammation, influenza A virus, orthopoxvirus, viral pneumonia
Research Division:Biological Sciences
Research Group:Microbiology
Research Field:Virology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Efficacy of medications
UTAS Author:Pandey, P (Mrs Pratikshya Pandey)
UTAS Author:Karupiah, G (Associate Professor Guna Karupiah)
ID Code:143376
Year Published:2021
Web of Science® Times Cited:2
Deposited By:Medicine
Deposited On:2021-03-14
Last Modified:2021-03-15

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